Hydrochloric Acid → HCID 59441879, compound

HRID 1014463Notes

Reaction equation

HRID 1014463 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:14][CH3:15])=[C:10]([NH2:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].Cl[C:17]1[N:18]=[C:19]([NH:36][C:37]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:38]=2[C:39]([NH2:41])=[O:40])[C:20]2[CH:25]=[CH:24][N:23]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:21]=2[N:22]=1.Cl.O1CCOCC1.[NH4+].[OH-]>FC(F)(F)CO.C1COCC1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:14][CH3:15])=[C:10]([NH:13][C:17]3[N:18]=[C:19]([NH:36][C:37]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:38]=4[C:39]([NH2:41])=[O:40])[C:20]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=5)(=[O:27])=[O:28])[C:21]=4[N:22]=3)[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 312751,4-DioxaneHCID 594418241-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)ethan-1-oneHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Product 1

HCID 59441879HCID 59441879, compound

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of 1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (212 mg, 2 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (836 mg, 1.8 mmol), KI (5.6 mg, 0.03 mmol) in 2,2,2-trifluoroethanol (10 mL) was treated with a 4 N HCl solution in dioxane (1.8 mL, 7.2 mmol). The reaction mixture was heated at 80° C. overnight in a sealed vessel, then was allowed to cool to rt Half of the reaction mixture was diluted with THF (100 mL) and a 27% aqueous NH4OH solution (100 mL). After stirring at rt overnight the reaction mixture was concentrated to dryness. The residue was sonicated in CH2Cl2 (10 mL), then filtered. The filtrate was purified by silica gel chromatography using 8-10% THF/CH2Cl2 to obtain 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-fluorobenzamide as a yellow solid (192 mg, 34% for 2 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 3H), 2.35 (s, 3H), 3.19 (t, J=8.33 Hz, 2H), 3.73 (s, 3H), 4.15 (t, J=8.33 Hz, 2H), 6.50 (d, J=3.85 Hz, 1H), 6.92 (t, J=9.25 Hz, 1H), 7.04 (s, 1H), 7.15-7.40 (m, 4H), 7.90-7.99 (m, 3H), 8.02 (s, 1H), 8.10 (d, J=8.61 Hz, 1H), 8.16 (s, 1H), 8.24 (s, 1H), 10.49 (s, 1H); ESIMS (M+H)+=630.13.

Workup

  1. temperatureto cool to rt Half of the reaction mixture
  2. concentrationwas concentrated to dryness
  3. customThe residue was sonicated in CH2Cl2 (10 mL)
  4. filtrationfiltered
  5. customThe filtrate was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a064ee7c9c004004844c2d35aaa8808c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…