Ammonium Hydroxide → N-(3-{5-(2-Amino-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

HRID 239446Notes

Reaction equation

HRID 239446 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][C@H:17]([CH3:19])[O:16][C@H:15]([CH3:20])[CH2:14]3)=[N:10][C:9]=2[C:21]2[C:22]([F:39])=[C:23]([NH:27][S:28]([C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[F:38])(=[O:30])=[O:29])[CH:24]=[CH:25][CH:26]=2)[CH:5]=[CH:4][N:3]=1.[NH4+:40].[OH-]>O1CCOCC1>[NH2:40][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][C@H:17]([CH3:19])[O:16][C@H:15]([CH3:20])[CH2:14]3)=[N:10][C:9]=2[C:21]2[C:22]([F:39])=[C:23]([NH:27][S:28]([C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[F:38])(=[O:30])=[O:29])[CH:24]=[CH:25][CH:26]=2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 57989877N-(3-{5-(2-Chloro-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamide

Product 1

HCID 57990068N-(3-{5-(2-Amino-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamideYield 75%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a pressure vessel was placed N-(3-{5-(2-chloro-4-pyrimidinyl)-2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-1,3-thiazol-4-yl}-2-fluorophenyl)-2,5-difluorobenzenesulfonamide (0.30 g, 0.503 mmol) and NH4OH (3 mL, 77 mmol) and 1,4-dioxane (3 mL) were added. The vessel was sealed and heated at 100° C. for 18 h. The reaction was cooled, concentrated onto silica and the residue was column chromatographed to give the title compound was obtained (0.22 g, 75% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.77 (br. s., 1H), 7.82 (d, J=5.3 Hz, 1H), 7.46-7.65 (m, 3H), 7.37-7.46 (m, 1H), 7.27 (t, J=6.7 Hz, 2H), 6.54 (br. s., 2H), 5.62 (d, J=5.3 Hz, 1H), 3.77 (d, J=12.2 Hz, 2H), 3.60-3.73 (m, 2H), 2.73 (t, J=11.6 Hz, 2H), 1.14 (d, J=6.0 Hz, 6H). m/z (ES+): 577 [M+H]+.

Workup

  1. customIn a pressure vessel was placed
  2. customThe vessel was sealed
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated onto silica
  5. customchromatographed

Sources & evidence

ORD record
ord-41dc09100eeb449eb31a1ab471577ac6
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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