2-Amino-4-methoxybenzoic acid → 4-Fluoro-2-(4-((3S,5R)-5-(hydroxymethyl)pyrrolidin-3-ylamino)-7-methoxyquinazolin-2-yl)phenol

HRID 2189233Notes

Reaction equation

HRID 2189233 reaction equation
NC1C=C(OC)C=CC=1C(O)=O.COC([C@H]1C[C@H](N)CN1C(OC(C)(C)C)=O)=O.FC1C=CC(O)=C(B(O)O)C=1.[F:41][C:42]1[CH:43]=[CH:44][C:45]([OH:77])=[C:46]([C:48]2[N:57]=[C:56]([NH:58][C@@H:59]3[CH2:63][N:62](C(OC(C)(C)C)=O)[C@@H:61]([C:71](OC)=[O:72])[CH2:60]3)[C:55]3[C:50](=[CH:51][C:52]([O:75][CH3:76])=[CH:53][CH:54]=3)[N:49]=2)[CH:47]=1>>[F:41][C:42]1[CH:43]=[CH:44][C:45]([OH:77])=[C:46]([C:48]2[N:57]=[C:56]([NH:58][C@H:59]3[CH2:60][C@H:61]([CH2:71][OH:72])[NH:62][CH2:63]3)[C:55]3[C:50](=[CH:51][C:52]([O:75][CH3:76])=[CH:53][CH:54]=3)[N:49]=2)[CH:47]=1

Participants

5

Reactant 4

HCID 3510102-Amino-4-methoxybenzoic acidHCID 15194991-tert-Butyl 2-methyl (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylateHCID 37724765-Fluoro-2-hydroxyphenylboronic acidHCID 136337397(2R,4S)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)-7-methoxyquinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 1359215244-Fluoro-2-(4-((3S,5R)-5-(hydroxymethyl)pyrrolidin-3-ylamino)-7-methoxyquinazolin-2-yl)phenol

Procedure

The title compound was prepared using methods analogous to those described in Synthesis 80-A, 30-A, 76-B and 89-B, replacing 2-amino-5-methoxybenzoic acid with 2-amino-4-methoxybenzoic acid in Synthesis 80-A, replacing (S)-(−)-1-boc-3-aminopyrrolidine with (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester in Synthesis 30-A, replacing 2-hydroxyphenylboronic acid with 5-fluoro-2-hydroxyphenylboronic acid in Synthesis 76-B (using the crude Boc-protected amine in Synthesis 89-B), and replacing (2R,4S)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate with (2R,4S)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)-7-methoxyquinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate in Synthesis 89-B.

Sources & evidence

ORD record
ord-4d06a65a5b4a4d1e9a6c63cbc394bfbe
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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