Methanol → HCID 178464110, compound

HRID 1014468Notes

Reaction equation

HRID 1014468 reaction equation
[CH2:1]([N:3]([CH2:39][CH3:40])[CH2:4][C:5]([N:7]1[C:15]2[C:10](=[CH:11][C:12]([O:37][CH3:38])=[C:13]([NH:16][C:17]3[NH:22][C:21]4=[N:23][CH:24]=[CH:25][C:20]4=[C:19]([NH:26][C:27]4[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:28]=4[C:29]([NH2:31])=[O:30])[N:18]=3)[CH:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:2].[CH3:41]N.CO.C[O-].[Na+]>C1COCC1>[CH2:39]([N:3]([CH2:1][CH3:2])[CH2:4][C:5]([N:7]1[C:15]2[C:10](=[CH:11][C:12]([O:37][CH3:38])=[C:13]([NH:16][C:17]3[NH:22][C:21]4=[N:23][CH:24]=[CH:25][C:20]4=[C:19]([NH:26][C:27]4[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:28]=4[C:29]([NH:31][CH3:41])=[O:30])[N:18]=3)[CH:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:40]

Participants

6

Reactant 4

HCID 887MethanolHCID 6329MethylamineHCID 10942334Sodium MethoxideHCID 178464109HCID 178464109, compound

Product 1

HCID 178464110HCID 178464110, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The remaining half of the reaction mixture from the preparation of 2-[(2-{[1-(N,N-diethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide was diluted with THF (100 mL) and a solution of methylamine (1M in THF, 10 mL). After 4 h the reaction mixture was concentrated, the resulting residue was sonicated in CH2Cl2 (10 mL) and filtered. The filtrate was purified by silica gel chromatography using 0-5% MeOH (containing 0.2% NH3)/CH2Cl2. The product was dissolved in THF (10 mL) and MeOH (20 mL) and treated with a solution of sodium methoxide (0.5M in MeOH, 4 mL, 2 mmol). The reaction mixture was stirred for 2 days, then concentrated onto Celite and purified by silica gel chromatography using 4% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-[(2-{[1-(N,N-diethylglycyl)-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 yellow solid (60 mg, 30% for 3 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98 (t, J=7.15 Hz, 6H) 2.58 (q, J=6.72 Hz, 4H) 2.80 (d, J=4.77 Hz, 3H), 3.12 (t, J=8.43 Hz, 2H),3.77 (s, 3H), 4.24 (t, J=8.43 Hz, 2H), 6.27 (dd, J=3.30, 1.83 Hz, 1H), 6.76-7.03 (m, 3H), 7.26-7.39 (m, 1H), 7.57 (s, 1H), 8.36 (d, J=8.43 Hz, 1H), 8.54 (s, 1H), 8.62 (s, 1H), 10.16 (s, 1H), 11.26 (s, 1H), a CH2 signal with 2 protons is missing, may overlap with water peak in sample; ESIMS (M+H)+=561.27.

Workup

  1. concentrationAfter 4 h the reaction mixture was concentrated
  2. customthe resulting residue was sonicated in CH2Cl2 (10 mL)
  3. filtrationfiltered
  4. customThe filtrate was purified by silica gel chromatography
  5. dissolutionThe product was dissolved in THF (10 mL)
  6. concentrationconcentrated onto Celite
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-2fdd5c4732a04bd79da3b1937da0bb56
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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