Ammonium Hydroxide → 5-bromo-2-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

HRID 1014435Notes

Reaction equation

HRID 1014435 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:13]3[CH:21]=[CH:20][N:19]([S:22]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)(=[O:24])=[O:23])[C:14]=3[N:15]=[C:16](Cl)[N:17]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8].[OH-].[NH4+].[CH3:34][CH:35]([N:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:49]=[CH:48][C:46]([NH2:47])=[C:45]([O:50][CH3:51])[CH:44]=2)[CH2:39][CH2:38]1)[CH3:36]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:13]3[CH:21]=[CH:20][N:19]([S:22]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)(=[O:24])=[O:23])[C:14]=3[N:15]=[C:16]([NH:47][C:46]3[CH:48]=[CH:49][C:43]([N:40]4[CH2:41][CH2:42][N:37]([CH:35]([CH3:34])[CH3:36])[CH2:38][CH2:39]4)=[CH:44][C:45]=3[O:50][CH3:51])[N:17]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8]

Participants

4

Reactant 3

HCID 14923Ammonium HydroxideHCID 457907394-(4-Isopropylpiperazin-1-YL)-2-methoxyphenylamineHCID 866441945-bromo-2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

Product 1

HCID 673163425-bromo-2-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamideYield 73.1%

Procedure

According to General Protocol III/Step A & B, 5-bromo-2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.5 g, 3.69 mmol), 27% aqueous ammonium hydroxide, and 4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)aniline (0.550 g, 3.32 mmol) were combined to afford 5-bromo-2-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide as a pale yellow solid (1.78 g). An aliquot of 5-bromo-2-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (0.340 g) was detosylated according to the General Protocol III/Step C to afford 5-bromo-2-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (0.204 g, 58% yield, 3 steps); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98 (d, J=6.41 Hz, 6H), 2.56 (s, 4H), 2.63 (d, J=6.23 Hz, 1H), 3.07 (s, 4H), 3.26 (s, 3H), 6.19 (dd, J=3.30, 1.83 Hz, 1H), 6.45 (d, J=8.97 Hz, 1H), 6.59 (d, J=2.01 Hz, 1H), 6.91 (d, J=2.20 Hz, 1H), 7.41 (s, 1H), 7.51 (dd, J=9.06, 2.29 Hz, 1H), 7.75-7.84 (m, 2H), 7.96 (d, J=2.20 Hz, 1H), 8.35 (s, 1H), 8.88 (d, J=8.97 Hz, 1H), 11.26 (s, 1H), 11.85 (s, 1H). ESIMS (M+H)+=580.

Sources & evidence

ORD record
ord-ceb531af4f4043b78fe270c0f3b3780c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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