At the time of Abraham's calling to sacrifice his only son Gen. 22:2, Isaac was his only son. In the previous chapter at Gen. 21:9-12, Ishmael had already been cast out; Hagar was raising him. It is in Isaac that Abraham's seed was defined, called, identified, proclaimed, (Strong's H7121).
"Wherefore she said unto Abraham, Cast out this bondwoman and her son: for the son of this bondwoman shall not be heir with my son, even with Isaac. And the thing was very grievous in Abraham's sight because of his son. And God said unto Abraham, Let it not be grievous in thy sight because of the lad, and because of thy bondwoman; in all that Sarah hath said unto thee, hearken unto her voice; for in Isaac shall thy seed be called."
To be sure, in Gen. 21:13 Ishmael is also said to be of Abraham's seed, but it is in Isaac that Abraham's seed is called (KJV, YLT), named (ESV, RSV), reckoned (NIV).
EDIT TO ADD RE Heb. 11:17 and only begotten and verse 18 explanation thereof.
By faith Abraham, when he was tried, offered up Isaac: and he that had received the promises offered up his only begotten son, Of whom it was said, That in Isaac shall thy seed be called:
EDIT TO ADD re "ONLY BEGOTTEN":
Monogenes has two primary definitions, "pertaining to being the only one of its kind within a specific relationship" and "pertaining to being the only one of its kind or class, unique in kind".[1] Thus monogenēs (μονογενὴς) may be used both as an adjective monogenēs pais, meaning unique and special.[2] Its Greek meaning is often applied to mean "one of a kind, one and only". Monogenēs (μονογενὴς) may be used both as an adjective monogenēs pais, only child, or only legitimate child, special child, and also on its own as a noun; o monogenēs "the only one", or "the only legitimate child".[3]
The word is used in Hebrews 11:17-19 to describe Isaac, the son of Abraham. However Isaac was not the only-begotten son of Abraham, but was the chosen, having special virtue. https://en.wikipedia.org/wiki/Monogen%C4%93s
