Formamidine → HCID 178499612, compound
Reaction equation
[NH:1]1C2=NC=CC2=C[NH:3][CH2:2]1.C([O:12][C:13](=O)[CH:14]([C:21]([O:23]CC)=O)[CH2:15][C:16]([O:18][CH2:19]C)=[O:17])C.C(N)=N>>[CH3:19][O:18][C:16](=[O:17])[CH2:15][C:14]1[C:21]([OH:23])=[N:1][CH:2]=[N:3][C:13]=1[OH:12]Participants
Procedure
Dihydropyrrolo[2,3-d]pyrimidine derivatives may be prepared as shown in FIG. 39. 2-Ethoxycarbonyl-succinic acid diethyl ester (200) was heated with formamidine to provide (4,6-Dihydroxypyrimidin-5-yl)-acetic acid methyl ester (201). Halogenation of compound (201) with (for example) POCl3 gave the dichloropyrimidine derivative (202). Treating compound (142) with base (e.g., KH) in THF and an electrophile R3X affords the intermediate (203). Reduction with an agent such as DIBAL-H gives the alcohol, which was activated with (for example) MsCl in the presence of base (e.g., TEA) to provide the mesylate intermediate (204). Treating the mesylate (204) with (for example) p-methoxybenzylamine yielded the dihydropyrrolo[2,3-d]pyrimidine derivative (205). SNAr reaction of the compound (205) with 1-Boc-piperazine formed the intermediate (206). Deprotection of the compound (206) with acid (e.g., TFA) gave the free amine (207). Amide coupling of the free amine (207) with an appropriately substituted/protected amino acid and followed by deprotection (if necessary) gave the product (208).
Sources & evidence
- ORD record
- ord-28d65893568c4da4ad070e08ec3259ec
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08680114B2
Reaction notes
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