Ammonium Hydroxide → HCID 59441804, compound

HRID 1014543Notes

Reaction equation

HRID 1014543 reaction equation
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[C:5]=2[N:4]=1.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH2:47])[CH:45]=2)[CH2:40][C@H:39]1[CH3:50])=[O:37])[CH3:34].[NH4+:51].[OH-].C([O-])(O)=O.[Na+]>FC(F)(F)CO.CCOC(C)=O>[CH3:34][N:33]([CH3:32])[CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH:47][C:3]3[N:16]=[C:7]([NH:8][C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=4[C:15]([NH2:51])=[O:17])[C:6]4[CH:19]=[CH:20][N:21]([S:22]([C:25]5[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=5)(=[O:24])=[O:23])[C:5]=4[N:4]=3)[CH:45]=2)[CH2:40][C@H:39]1[CH3:50])=[O:37]

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 516892Sodium BicarbonateHCID 59441624HCID 59441624, compoundHCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

Product 1

HCID 59441804HCID 59441804, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (600 mg, 1.252 mmol) and (2R)-1-[(dimethylamino)acetyl]-2-methyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (330 mg, 1.252 mmol) in 2,2,2-trifluoroethanol (10 mL) was stirred at rt for 18 h. The resulting bright green slurry was divided into two equal batches. One of the batches was treated with a 27% aqueous NH4OH solution (10 mL). The resulting orange slurry was stirred at rt for 2 days, then was diluted with EtOAc (50 mL) and a saturated NaHCO3 solution (50 mL). The organic layer was washed with a saturated NaCl solution (50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to afford 2-({2-{[(2R)-1-(N,N-dimethylglycyl)-2-methyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a yellow solid (249 mg, 58%). 1H NMR (400 MHz, DMSO-d5) δ ppm 1.18-1.32 (m, 3H), 2.27 (br s, 6H), 2.33 (s, 3H), 2.63 (d, J=16.12 Hz, 1H), 3.14 (d, J=14.65 Hz, 1H), 3.27-3.51 (m, 2H), 3.76 (s, 3H), 4.75-4.87 (m, 1H), 6.53 (d, J=4.03 Hz, 1H), 6.94 (t, J=9.34 Hz, 1H), 7.06 (s, 1H), 7.14-7.42 (m, 4H), 7.72-8.04 (m, 4H), 8.07 (d, J=8.24 Hz, 1H), 8.18 (s, 1H), 8.25 (s, 1H), 10.46 (s, 1H). ESIMS (M+H)+=687.26.

Workup

  1. washThe organic layer was washed with a saturated NaCl solution (50 mL)
  2. concentrationconcentrated onto Celite
  3. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-7768d45db5de4afe9379163c2c2e47e5
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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