Sodium Methoxide → HCID 178485528, compound

HRID 1014466Notes

Reaction equation

HRID 1014466 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:45][CH3:46])=[C:10]([NH:13][C:14]3[N:15]=[C:16]([NH:33][C:34]4[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:35]=4[C:36]([NH:38][CH3:39])=[O:37])[C:17]4[CH:22]=[CH:21][N:20](S(C5C=CC(C)=CC=5)(=O)=O)[C:18]=4[N:19]=3)[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C[O-].[Na+]>CO.C1COCC1.CCOC(C)=O.[Na+].[Cl-]>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:45][CH3:46])=[C:10]([NH:13][C:14]3[NH:19][C:18]4=[N:20][CH:21]=[CH:22][C:17]4=[C:16]([NH:33][C:34]4[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:35]=4[C:36]([NH:38][CH3:39])=[O:37])[N:15]=3)[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

7

Reactant 2

HCID 10942334Sodium MethoxideHCID 59442082HCID 59442082, compound

Product 1

HCID 178485528HCID 178485528, compoundYield 75%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 5234Sodium ChlorideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-({2-{[1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (130 mg, 0.2 mmol) in MeOH (10 mL) and THF (20 mL) was treated with a solution of sodium methoxide (0.5M in MeOH, 4 mL, 2 mmol). The resulting mixture was stirred at rt overnight, then diluted with EtOAc (100 mL) and saturated NaCl solution. The organic layer was washed with a saturated NaHCO3 solution, concentrated onto Celite and purified by silica gel chromatography using 0-5% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-[(2-{[1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide as a beige solid (73 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.13 (s, 3H) 2.80 (d, J=4.4 Hz, 3H), 3.12 (t, J=8.42 Hz, 2H), 3.78 (s, 3H), 4.10 (t, J=8.42 Hz, 2H), 6.27 (d, J=1.28 Hz, 1H), 6.86-6.98 (m, 3H), 7.28-7.37 (m, 1H), 7.55 (s, 1H), 8.34 (d, J=8.61 Hz, 1H), 8.55 (br s, 1H), 8.63 (s, 1H), 10.14 (s, 1H), 11.27 (s, 1H); ESIMS (M+H)+=489.98.

Workup

  1. washThe organic layer was washed with a saturated NaHCO3 solution
  2. concentrationconcentrated onto Celite
  3. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-160227e2ca364bb3af9cd5059b872dec
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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