Triethylamine → 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamide

HRID 222980Notes

Reaction equation

HRID 222980 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)=O)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:22]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:37].C[CH2:39][N:40](CC)CC.Cl.Cl.[NH:47]1[CH:51]=[CH:50][N:49]=[C:48]1NC>C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:40][CH2:39][C:48]3[NH:47][CH:51]=[CH:50][N:49]=3)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:22]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:37]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 574345493-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methyl-N-1,3-thiazol-2-ylbenzamideHCID 57434550(1H-Imidazol-2-yl)-methylamine dihydrochloride

Product 1

HCID 119481803-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of 3-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methyl-N-1,3-thiazol-2-ylbenzamide (1.37 g, 2.54 mmol) in DCM (127 mL) were added Et3N (1.78 mL, 12.7 mmol) and (1H-imidazol-2-yl)-methylamine dihydrochloride (0.625 g, 3.81 mmol). The mixture was stirred at room temperature over night and concentrated under vacuum. Flash chromatography [mobile phase DCM/DCM (90)+MeOH(7)+NH4OH(3)] then provided the title compound as a white solid 1.23 g (85%). MS (ES) m/z 571 (M+H)+; 1H-NMR (MeOD) δ 2.16 (s, 1.5H), 2.32 (s, 1.5H), 3.18 (d, J=4.4 Hz, 0.75H), 4.11 (d, J=5.2 Hz, 0.25H), 4.21 (d, J=5.0 Hz, 1H), 4.50 (m, 1H), 6.37 (d, J=9.6 Hz, 1H), 6.85 (s, 2H), 7.29 (s, 2H), 7.43 (m, 2H), 7.57 (m, 3H), 8.18 (m, 3 H), 11.60 (s, br, 1H), 12.64 (s, br, 2H).

Workup

  1. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5efc4cc4842a4f0aade0ca4589cedc31
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

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