N,N-Dimethylglycine → (3R,5R)-5-[({4-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)-methyl]-1-(N,N-dimethylglycyl)pyrrolidin-3-ol

HRID 1443020Notes

Reaction equation

HRID 1443020 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[F:29])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:24][CH3:25])=[CH:13][C:14]=2[O:16][CH2:17][C@@H:18]2[NH:22][CH2:21][C@H:20]([OH:23])[CH2:19]2)[N:9]=[CH:8][N:7]=1.[CH3:30][N:31]([CH3:36])[CH2:32][C:33](O)=[O:34]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[F:29])[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:24][CH3:25])=[CH:13][C:14]=2[O:16][CH2:17][C@@H:18]2[N:22]([C:33](=[O:34])[CH2:32][N:31]([CH3:36])[CH3:30])[CH2:21][C@H:20]([OH:23])[CH2:19]2)[N:9]=[CH:8][N:7]=1

Participants

3

Reactant 2

HCID 673N,N-DimethylglycineHCID 68675637(3R,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol

Product 1

HCID 11420722(3R,5R)-5-[({4-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)-methyl]-1-(N,N-dimethylglycyl)pyrrolidin-3-olYield 72%

Procedure

The procedure described in Example 32 was repeated using (3R,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol (209 mg) with N,N-dimethylglycine (57 mg) to give the title compound as a white solid in 72% yield; NMR spectrum (DMSO-d6) 10.03 (s, 1H), 8.46 (s, 1H), 8.19 (dd, 1H), 7.76-7.71 (m, 1H), 7.43 (t, 1H), 6.83 (d, 1H), 6.75 (d, 1H), 5.27-5.26 (m, 1H), 4.72-4.67 (m, 1H), 4.61-4.56 (m, 1H), 4.41-4.40 (m, 1H), 4.34-4.29 (m, 1H), 3.93 (s, 3H), 3.78 (dd, 1H), 3.52 (br d, 1H), 3.14 (d, 1H), 2.99 (d, 1H), 2.26-2.17 (m, 7H), 1.95-1.90 (m, 1H); Mass spectrum MH+ 504.

Sources & evidence

ORD record
ord-2c0454aa67304230b24f00ce44aa1420
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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