Sodium Chloride → HCID 178485527, compound

HRID 1014547Notes

Reaction equation

HRID 1014547 reaction equation
[CH3:1][N:2]([CH3:50])[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][C@@H:7]1[CH3:49])=[O:5].[OH-].[Na+].[Na+].[Cl-]>O1CCOCC1.CCOC(C)=O>[CH3:50][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][C@@H:7]1[CH3:49])=[O:5]

Participants

6

Reactant 3

HCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 59441724HCID 59441724, compound

Product 1

HCID 178485527HCID 178485527, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-({2-{[(2S)-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-fluoro-N-methylbenzamide (254 mg, 0.362 mmol) in dioxane (10 mL) and a 2M aqueous NaOH solution (2 mL) was heated at 80° C. for 6 h. The resulting mixture was allowed to cool to rt, diluted with EtOAc (50 mL) and a saturated NaCl solution (10 mL). The organic layer was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to afford 2-[(2-{[(2S)-1-(N,N-dimethylglycyl)-2-methyl-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 pink solid (144 mg, 73%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (d, J=5.49 Hz, 3H), 2.27 (s, 6H), 2.59 (d, J=15.57 Hz, 1H), 2.80 (d, J=4.40 Hz, 3H), 3.08 (d, J=14.28 Hz, 1H), 3.21-3.46 (m, 2H), 3.80 (s, 3H), 4.71-4.85 (m, 1H), 6.27-6.34 (m, 1H), 6.83-7.08 (m, 3H), 7.26-7.44 (m, 1H), 7.54 (s, 1H), 8.33 (d, J=8.06 Hz, 1H), 547.40; Optical rotation −11.4 (1 mg/mL MeOH, rt).

Workup

  1. concentrationThe organic layer was concentrated onto Celite
  2. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-368979b06e944f7fa7623c8b990a1120
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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