5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one → N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide

HRID 1014532Notes

Reaction equation

HRID 1014532 reaction equation
Cl[C:2]1[N:15]2[C:6](=[N:7][C:8]3[C:13]([C:14]2=[O:16])=[C:12]([F:17])[CH:11]=[CH:10][CH:9]=3)[C:5]2[CH:18]=[CH:19][N:20]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[C:4]=2[N:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]([N:40]([CH3:47])[C:41](=[O:46])[CH2:42][N:43]([CH3:45])[CH3:44])[CH:35]=[CH:36][C:37]=1[O:38][CH3:39]>O1CCCC1>[F:17][C:12]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:13]=1[C:14](=[O:16])[N:15]1[C:2]([NH:31][C:32]3[CH:33]=[C:34]([N:40]([CH3:47])[C:41](=[O:46])[CH2:42][N:43]([CH3:45])[CH3:44])[CH:35]=[CH:36][C:37]=3[O:38][CH3:39])=[N:3][C:4]3[N:20]([S:21]([C:24]4[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[CH:19]=[CH:18][C:5]=3[C:6]1=[N:7]2

Participants

4

Reactant 2

HCID 594416275-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-oneHCID 59441934N1-[3-amino-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide

Product 1

HCID 67316278N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamideYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (2.00 g, 4.17 mmol) and N1-[3-amino-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (1.040 g, 4.38 mmol) in tetrahydrofuran (75 ml) was maintained at 65° C. for 16 hours in a sealed pressure tube. The reaction was cooled, taken to a residue under reduced pressure, and partitioned between dichloromethane/saturated sodium bicarbonate with 2,2,2-trifluoroethanol added until all solids had dissolved. The organic layer was separated, taken to a residue under reduced pressure, and triturated with diethyl ether to afford analytically pure N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (2.55 g, 3.96 mmol, 95% yield) as a pale yellow solid. ESIMS (M+H)+=644.

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between dichloromethane/saturated sodium bicarbonate with 2,2,2-trifluoroethanol
  3. additionadded until all solids
  4. dissolutionhad dissolved
  5. customThe organic layer was separated
  6. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-d68e66e3d5684b9a9d99da4344d76a63
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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