Methylamine → HCID 178485308, compound

HRID 1014531Notes

Reaction equation

HRID 1014531 reaction equation
[CH3:1][N:2]([CH3:37])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:35][CH3:36])=[C:12]([NH:15][C:16]3[NH:21][C:20]4=[N:22][CH:23]=[CH:24][C:19]4=[C:18]([NH:25][C:26]4[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=4[C:28]([NH2:30])=[O:29])[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[CH3:38]N.[OH-].[K+]>CCOC(C)=O>[CH3:1][N:2]([CH3:37])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:35][CH3:36])=[C:12]([NH:15][C:16]3[NH:21][C:20]4=[N:22][CH:23]=[CH:24][C:19]4=[C:18]([NH:25][C:26]4[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=4[C:28]([NH:30][CH3:38])=[O:29])[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 14797Potassium HydroxideHCID 178486466HCID 178486466, compound

Product 1

HCID 178485308HCID 178485308, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

The remaining reaction mixture from the preparation of 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide was diluted with a solution of methylamine (2M in THF 15 mL, 30 mmol). The resulting mixture maintained at rt for 2 days and was diluted with EtOAc (200 mL), washed with a saturated NaHCO3 solution (200 mL) and a saturated NaCl solution (125 mL). The organic layer was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2, followed by trituration using a mixture of CH2Cl2 and Et2O. The crude product was dissolved in dioxane (13 mL) and was treated with a 1M aqueous KOH solution (1.121 mL, 1.121 mmol). The resulting mixture was heated at 90° C. for 6 h and was allowed to cool to rt and diluted with EtOAc (100 mL), washed with a saturated NaHCO3 solution (50 mL) and a saturated NaCl solution (50 mL). The organic layer was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-methylbenzamide as a beige solid (70 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.26 (s, 6H), 2.83 (d, J=4.40 Hz, 3H), 3.04-3.28 (m, 4H), 3.78 (s, 3H), 4.18 (t, J=8.33 Hz, 2H), 6.23-6.38 (m, 1H), 6.87-7.07 (m, 3H), 7.60 Hz, 1H), 7.60 (s, 1H), 7.72 (d, 7.33 Hz, 1H), 8.64 (s, 1H), 8.67-8.81 (m, 1H), 8.90 (d, J=8.24 Hz, 1H), 11.26 (s, 1H), 11.73 (s, 1H); ESIMS (M+H)+=515.33.

Workup

  1. customThe remaining reaction mixture
  2. washwashed with a saturated NaHCO3 solution (200 mL)
  3. concentrationThe organic layer was concentrated onto Celite
  4. custompurified by silica gel chromatography
  5. additiona mixture of CH2Cl2 and Et2O
  6. dissolutionThe crude product was dissolved in dioxane (13 mL)
  7. temperatureThe resulting mixture was heated at 90° C. for 6 h
  8. temperatureto cool to rt
  9. washwashed with a saturated NaHCO3 solution (50 mL)
  10. concentrationThe organic layer was concentrated onto Celite
  11. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-e6a9aaf1f6e740a0ae18d1364305a668
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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