Diisopropylethylamine → (S)-N-(1-{7-Fluoro-8-methyl-2-[4-(pyridin-2-yl)piperazin-1-yl]quinolin-3-yl}ethyl)pyrido[3,2-d]pyrimidin-4-amine

HRID 242143Notes

Reaction equation

HRID 242143 reaction equation
[F:1][C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:25]([NH2:27])[CH3:26])[C:8]([N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:15][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1.Cl[C:29]1[C:30]2[N:38]=[CH:37][CH:36]=[CH:35][C:31]=2[N:32]=[CH:33][N:34]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[F:1][C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:25]([NH:27][C:29]3[C:30]4[N:38]=[CH:37][CH:36]=[CH:35][C:31]=4[N:32]=[CH:33][N:34]=3)[CH3:26])[C:8]([N:13]3[CH2:14][CH2:15][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:17][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 131016394-Chloropyrido(3,2-d)pyrimidineHCID 71183465(S)-1-{7-fluoro-8-methyl-2-[4-(pyridin-2-yl)piperazin-1-yl]quinolin-3-yl}ethanamine

Product 1

HCID 52938132(S)-N-(1-{7-Fluoro-8-methyl-2-[4-(pyridin-2-yl)piperazin-1-yl]quinolin-3-yl}ethyl)pyrido[3,2-d]pyrimidin-4-amineYield 58.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Following the procedure described for Intermediate 13, Intermediate 14 (530 mg, 1.1 mmol) and TFA (3 mL) in DCM (6 mL) afforded (S)-1-{7-fluoro-8-methyl-2-[4-(pyridin-2-yl)piperazin-1-yl]quinolin-3-yl}ethanamine as a white foam, which was used in the next step without any further purification. Following the procedure described for Example 5, (S)-1-{7-fluoro-8-methyl-2-[4-(pyridin-2-yl)piperazin-1-yl]quinolin-3-yl}ethanamine (60 mg, 0.16 mmol), 4-chloropyrido[3,2-d]pyrimidine (33 mg, 0.19 mmol) and DIPEA (0.14 mL, 0.8 mmol) in NMP (1.2 mL) afforded the title compound (46 mg, 58%) as a beige solid. δH (DMSO-d6) 8.94-8.89 (2H, m), 8.56 (1H, s), 8.52 (1H, s), 8.20-8.16 (2H, m), 7.91 (1H, dd, J 8.5, 4.3 Hz), 7.74 (1H, dd, J 8.9, 6.3 Hz), 7.65-7.55 (1H, m), 7.32 (1H, t, J 9.1 Hz), 6.96 (1H, d, J 8.6 Hz), 6.71 (1H, dd, J 7.1, 4.9 Hz), 5.95 (1H, m), 3.87-3.69 (6H, m), 3.33-3.23 (2H, m), 2.58 (3H, s), 1.68 (3H, d, J 6.7 Hz). LCMS (ES+) 495 (M+H)+, RT 3.09 minutes (Method 4).

Workup

  1. customwas used in the next step without any further purification

Sources & evidence

ORD record
ord-25a49efe58034fa5ae6b4d101d6af659
Source dataset
uspto-grants-2014_02
Patent number
US08653105B2

Reaction notes

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