Ammonium Hydroxide → 2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

HRID 1014443Notes

Reaction equation

HRID 1014443 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:54])[N:5]1[C:15]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][N:32]([S:35]([CH3:38])(=[O:37])=[O:36])[CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[CH:19][C:18]=3[O:39][CH3:40])=[N:14][C:13]3[N:41]([S:44]([C:47]4[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=4)(=[O:46])=[O:45])[CH:42]=[CH:43][C:12]=3[C:6]1=[N:7]2.[NH4+:55].[OH-]>O1CCCC1>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:7][C:6]2[C:12]3[CH:43]=[CH:42][N:41]([S:44]([C:47]4[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=4)(=[O:45])=[O:46])[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][CH:26]([N:29]5[CH2:30][CH2:31][N:32]([S:35]([CH3:38])(=[O:37])=[O:36])[CH2:33][CH2:34]5)[CH2:25][CH2:24]4)=[CH:19][C:18]=3[O:39][CH3:40])[N:5]=2)[C:3]=1[C:4]([NH2:55])=[O:54]

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 594419478-fluoro-5-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

Product 1

HCID 594421352-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamideYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8-fluoro-5-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (4.5 g, 5.81 mmol) and 30% aqueous NH4OH (75 mL, 5.81 mmol) and tetrahydrofuran (75 mL) was stirred at rt overnight in a 200 mL rb flask. The solution was extracted with ethyl acetate (250 mL) and brine (50 mL). The organic layers were dried over MgSO4, filtered, concentrated onto Celite and purified on SiO2 (1-10% MeOH in CH2Cl2 and 0.1% NH4OH) to afford 2-fluoro-6-({2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (2.78 g, 3.51 mmol, 60% yield) as a mixture with several other products. The desired product was the predominant component. The product weight was 2.78 grams. ESIMS (M+H)+=792.42 (100%). This material was used without further purification in the next step.

Workup

  1. extractionThe solution was extracted with ethyl acetate (250 mL) and brine (50 mL)
  2. dry with materialThe organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated onto Celite
  5. custompurified on SiO2 (1-10% MeOH in CH2Cl2 and 0.1% NH4OH)

Sources & evidence

ORD record
ord-21d2c6d7b9904b85b4ef71110a6d0e38
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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