Hydrochloric Acid → 3-{2-[(cyclopropylmethyl)amino]-5-(methylsulfonyl)phenyl}-1-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 633539Notes

Reaction equation

HRID 633539 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:7]=2[C:16]2[C:24]3[C:19](=[C:20]([O:25]C)[N:21]=[CH:22][CH:23]=3)[N:18]([CH3:27])[CH:17]=2)[CH2:3][CH2:2]1.Cl.O1CCOCC1>>[CH:1]1([CH2:4][NH:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:7]=2[C:16]2[C:24]3[CH:23]=[CH:22][NH:21][C:20](=[O:25])[C:19]=3[N:18]([CH3:27])[CH:17]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 90387888N-(cyclopropylmethyl)-2-(7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)-4-(methylsulfonyl)aniline

Product 1

HCID 903883093-{2-[(cyclopropylmethyl)amino]-5-(methylsulfonyl)phenyl}-1-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-oneYield 71%

Conditions

Temperature
70 °C

Procedure

The product from Example 44B (0.035 g, 0.091 mmol) and 4 M hydrogen chloride in dioxane (0.023 mL, 0.091 mmol) were combined and heated at 70° C. for 24 hours, cooled and concentrated. Purification by reverse phase chromatography (C18, CH3CN/water (0.1% TFA), 10-100%) afforded the title compound (0.024 g, 53%) as the TFA salt. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.95 (d, J=5.43 Hz, 1H) 7.62 (dd, J=8.82, 2.37 Hz, 1H) 7.45-7.48 (m, 2H) 6.86-6.91 (m, 1H) 6.84 (d, J=8.82 Hz, 1H) 6.21 (dd, J=6.78, 1.02 Hz, 1H) 5.50 (s, 1H) 4.12 (s, 3H) 3.09 (s, 3H) 3.05 (d, J=6.44 Hz, 2H) 0.95-1.14 (m, 1H) 0.38-0.45 (m, 2H) 0.17-0.24 (m, 2H). MS (ESI+) m/z 372 (M+H)+.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. customPurification by reverse phase chromatography (C18, CH3CN/water (0.1% TFA), 10-100%)

Sources & evidence

ORD record
ord-2c354f8687ff47e7908d5d745657aac7
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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