Potassium Hydroxide → HCID 178485533, compound

HRID 1014446Notes

Reaction equation

HRID 1014446 reaction equation
[CH3:1][N:2]([CH3:49])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:47][CH3:48])=[C:12]([NH:15][C:16]3[N:17]=[C:18]([NH:35][C:36]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:37]=4[C:38]([NH:40][CH3:41])=[O:39])[C:19]4[CH:24]=[CH:23][N:22](S(C5C=CC(C)=CC=5)(=O)=O)[C:20]=4[N:21]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[OH-].[K+]>O1CCOCC1.CCOC(C)=O>[CH3:49][N:2]([CH3:1])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:47][CH3:48])=[C:12]([NH:15][C:16]3[NH:21][C:20]4=[N:22][CH:23]=[CH:24][C:19]4=[C:18]([NH:35][C:36]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:37]=4[C:38]([NH:40][CH3:41])=[O:39])[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 59442024HCID 59442024, compound

Product 1

HCID 178485533HCID 178485533, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A light brown solution of 2-({2-{[1-(N,N-dimethylglycyl)-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 (26 g, 37.9 mmol) prepared in multiple batches as described in Step C above, in dioxane (900 mL) was treated with a 1N aqueous KOH solution (379 mL, 379 mmol). The resulting mixture was heated in a 90° C. bath for 3 hours. The resulting mixture was allowed to cool to room temperature, then was diluted with EtOAc (500 mL). The organic layer was separated and sequentially washed with a 2N aqueous NaOH solution (2×200 mL) and a saturated NaCl solution (300 mL), then concentrated to a thick slurry. The resulting slurry was filtered and the solid washed with Et2O. The filtrate was concentrated to a slurry, filtered, and combined with the previous residue 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]-6-fluoro-N-methylbenzamide as a light brown solid. (16.9 g, 84%, Yield). The remaining filtrate was concentrated and purified by flash silica gel chromatography using 1-10% MeOH (0.2% NH3)/CH2Cl2 affording an additional 1 g (5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.28 (s, 6H), 2.82 (d, J=4.40 Hz, 3H), 3.08-3.15 (m, 2H), 3.22 (s, 2H), 3.79 (s, 3H), 4.16 (t, J=8.25 Hz, 2H), 6.27 (d, J=1.83 Hz, 1H), 6.80-6.89 (m, 1H), 6.92 (d, J=2.20 Hz, 1H), 6.93 (s, 1H), 7.26-7.35 (m, 1H), 7.38 (s, 1H), 8.28 (s, 1H), 8.36 (d, J=8.43 Hz, 1H), 8.65 (s, 1H), 10.10 (s, 1H), 11.06 (s, 1H). ESIMS (M+H)=533.

Workup

  1. temperatureto cool to room temperature
  2. customThe organic layer was separated
  3. washsequentially washed with a 2N aqueous NaOH solution (2×200 mL)
  4. concentrationa saturated NaCl solution (300 mL), then concentrated to a thick slurry
  5. filtrationThe resulting slurry was filtered
  6. washthe solid washed with Et2O
  7. concentrationThe filtrate was concentrated to a slurry
  8. filtrationfiltered

Sources & evidence

ORD record
ord-589aabd808314c0a84faa1c671247928
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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