Ammonium Hydroxide → 2-fluoro-6-({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 1014430Notes

Reaction equation

HRID 1014430 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:47])[N:5]1[C:15]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]4)=[CH:19][C:18]=3[O:32][CH3:33])=[N:14][C:13]3[N:34]([S:37]([C:40]4[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=4)(=[O:39])=[O:38])[CH:35]=[CH:36][C:12]=3[C:6]1=[N:7]2.[OH-].[NH4+:49]>O1CCCC1.CCOC(C)=O>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:7][C:6]2[C:12]3[CH:36]=[CH:35][N:34]([S:37]([C:40]4[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=4)(=[O:38])=[O:39])[C:13]=3[N:14]=[C:15]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]4)=[CH:19][C:18]=3[O:32][CH3:33])[N:5]=2)[C:3]=1[C:4]([NH2:49])=[O:47]

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 673164628-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo [2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

Product 1

HCID 594420752-fluoro-6-({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 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (7.6 g, 11.6 mmol) in tetrahydrofuran (350 mL) was added 27% ammonium hydroxide (500 mL). The resulting biphasic mixture, was rapidly stirred for 24 hours, at which time no starting material was evident by TLC/LCMS. Three such reactions were combined, diluted with EtOAc, and the organic layers washed with saturated sodium chloride, dried over sodium sulfate, and taken to a residue under reduced pressure to give 2-fluoro-6-({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 (19.3 g, 28.7 mmol, 80% Yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.36 (s, 1 H), 8.04 (d, J=8.2 Hz, 1 H), 7.87-7.99 (m, 4 H), 7.79 (br. s., 2 H), 7.26-7.47 (m, 4 H), 6.87-7.06 (m, 1 H), 6.63 (d, J=2.4 Hz, 1 H), 6.47-6.58 (m, 2 H), 3.70-3.85 (m, 3 H), 3.05-3.19 (m, 4 H), 2.66 (quin, J=6.5 Hz, 1 H), 2.54-2.63 (m, 4 H), 2.32 (s, 3 H), 1.00 (d, J=6.6 Hz, 6 H). ESIMS (M+H)+=673.

Workup

  1. washthe organic layers washed with saturated sodium chloride
  2. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-fa7cd9a4c6eb433ab3d858740f66b018
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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