Pyrrolidine → N-[1-(3-fluorobenzyl)-1H-indazol-5-yl]-5-[(1R)-1-methyl-2-oxo-2-pyrrolidin-1-ylethoxy]-quinazolin-4-amine

HRID 1162243Notes

Reaction equation

HRID 1162243 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[O:26][C@H:27]([CH3:32])[C:28](OC)=[O:29])[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[O:26][C@H:27]([CH3:32])[C:28](=[O:29])[N:36]4[CH2:40][CH2:39][CH2:38][CH2:37]4)[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 86627837methyl (2R)-2-[(4-{[1-(3-fluorobenzyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

Product 1

HCID 16117486N-[1-(3-fluorobenzyl)-1H-indazol-5-yl]-5-[(1R)-1-methyl-2-oxo-2-pyrrolidin-1-ylethoxy]-quinazolin-4-amineYield 77.6%

Procedure

Using the same procedure as in Example 26, methyl (2R)-2-[(4-{[1-(3-fluorobenzyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate (250 mg, 0.53 mmol) was reacted with pyrrolidine (0.44 ml, 5.3 mmol) to give the title compound as a white solid (210 mg, 77%), except that the mixture was heated at 55° C. for 20 hours and purified by chromatography on silica gel (eluant: 3% methanol in DCM); NMR Spectrum 1.60 (d, 3H), 1.82 (m, 2H), 1.94 (m, 2H), 3.5-3.3 (m, 3H), 3.76 (m, 1H), 5.62 (q, 1H), 5.70 (s, 2H), 7.07 (m, 3H), 7.27 (d, 1H), 7.36 (m, 2H), 7.74 (m, 2H), 7.85 (m, 1H), 8.16 (s, 1H), 8.51 (s, 1H), 8.56 (s, 1H), 11.08 (br s, 1H); Mass spectrum 511.

Sources & evidence

ORD record
ord-2ef6e445b17442ddab798643231e732c
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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