Triethylamine → 4-(2-Cyclopropanesulfonylamino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

HRID 2075780Notes

Reaction equation

HRID 2075780 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH2:38])[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1.[CH:42]1([S:45](Cl)(=[O:47])=[O:46])[CH2:44][CH2:43]1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH:38][S:45]([CH:42]4[CH2:44][CH2:43]4)(=[O:47])=[O:46])[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 1363466894-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

Product 1

HCID 1363466934-(2-Cyclopropanesulfonylamino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 9D (4.0 g, 7.02 mmol) in anhydrous CH2Cl2 (100 mL) were added cyclopropanesulfonyl chloride (16D, (1.97 g, 14.03 mmol) and triethylamine (3.91 mL, 28.07 mmol), successively. The reaction mixture was stirred at rt overnight. It was concentrated to small volume and purified with silica column chromatography eluting with dichloromethane/EtOAc to give the title compound (17D) which was recrystallized from hexanes/acetone to provide compound 17D as white powder in ˜60% yield. 1H NMR (CDCl3, 500 MHz) δ 10.66 (s, 1H), 8.67 (s, 1H), 8.18 (s, 1H), 7.67 (d, 2H, J=8.0 Hz), 7.62 (s, 1H), 7.54 (d, 2H, J=8.0 Hz), 7.43 (s, 5H), 7.20 (d, 1H, J=8.5 Hz), 6.97 (d, 1H, J=9.0 Hz), 5.82 (d, 1H, J=8.0 Hz), 5.42 (d, 1H, J=9.0 Hz), 5.20 (s, 1H), 4.67 (d, 1H, J=11.5 Hz), 3.96 (s, 3H), 3.76 (d, 1H, J=11.5 Hz), 3.61 (br s, 2H), 3.44 (dd, 1H, J=12.0, 3.0 Hz), 2.93 (m, 1H), 2.41 (m, 1H), 1.15 (s, 2H), 0.94 (d, 2H, J=5.5 Hz). LCMS (ESI) m/z 696.19 (MNa+), 674.22 (MH+), 351.10 (100). HPLC: tR=4.95 min.

Workup

  1. concentrationIt was concentrated to small volume
  2. custompurified with silica column chromatography
  3. washeluting with dichloromethane/EtOAc

Sources & evidence

ORD record
ord-5ec27e5eff544530b0b63233a13fd633
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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