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Hydrochloric Acid → 9-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

HRID 1014434
Notes
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Reaction equation

HRID 1014434 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:23]=2[C:24](N)=[O:25])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[CH3:32][CH:33]([N:35]1[CH2:40][CH2:39][N:38]([C:41]2[CH:47]=[CH:46][C:44]([NH2:45])=[C:43]([O:48][CH3:49])[CH:42]=2)[CH2:37][CH2:36]1)[CH3:34].[I-].[K+].Cl.C(=O)(O)[O-].[Na+]>ClCCl>[F:31][C:28]1[CH:27]=[C:23]2[C:22](=[CH:30][CH:29]=1)[N:21]=[C:4]1[C:5]3[CH:10]=[CH:9][N:8]([S:11]([C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=4)(=[O:12])=[O:13])[C:6]=3[N:7]=[C:2]([NH:45][C:44]3[CH:46]=[CH:47][C:41]([N:38]4[CH2:39][CH2:40][N:35]([CH:33]([CH3:32])[CH3:34])[CH2:36][CH2:37]4)=[CH:42][C:43]=3[O:48][CH3:49])[N:3]1[C:24]2=[O:25]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 516892Sodium BicarbonateHCID 457907394-(4-Isopropylpiperazin-1-YL)-2-methoxyphenylamineHCID 866441892-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-5-fluorobenzamide

Product 1

HCID 67316701
9-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
Yield 76.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a pressurized vessel was added 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-5-fluorobenzamide (3.0 g, 6.54 mmol), 4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)aniline (2.11 g, 8.5 mmol), potassium iodide (<10 mg) and hydrochloric acid as a 4.0M solution in dioxanes (ca 10 mL). The resulting suspension was stirred until all solids had completely dissolved (24 hr.) The reaction was poured into into saturated sodium bicarbonate and diluted with dichloromethane. The organic layer was dried over sodium sulfate, volatiles removed under reduced pressure, and the solids triturated with diethyl ether to afford 9-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 (3.27 g, 76% yield) of sufficient purity for use in subsequent transformations. ESIMS (M+H)=656.

Workup

  1. dissolutionhad completely dissolved (24 hr.) The reaction
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customvolatiles removed under reduced pressure
  4. customthe solids triturated with diethyl ether

Sources & evidence

ORD record
ord-6291a63d17554ad4936f43b17a51adf0
Source dataset
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07981903B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes