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

HRID 2075779Notes

Reaction equation

HRID 2075779 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.[N:42]1([C:48](Cl)=[O:49])[CH2:47][CH2:46][O:45][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][C:48]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[O:49])[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 848104-Morpholinecarbonyl 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 1363466924-{2-[(Morpholine-4-carbonyl)-amino]-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 in anhydrous CH2Cl2 were slowly added 4-morpholinecarbonyl chloride (14D, 1.2 eq) and triethylamine (1.5 eq), 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 (15D) which was recrystallized from hexanes/acetone to provide compound 15D as white powder in ˜60% yield. 1H NMR (CDCl3, 500 MHz) δ 10.67 (s, 1H), 8.93 (s, 1H), 8.70 (s, 1H), 7.93 (d, 2H, J=7.5 Hz), 7.63 (s, 1H), 7.55 (d, 2H, J=7.5 Hz), 7.45 (s, 5H), 7.19 (d, 1H, J=8.0 Hz), 6.97 (d, 1H, J=8.0 Hz), 5.60 (d, 1H, J=6.5 Hz), 5.28 (s, 1H), 5.18 (d, 1H, J=6.5 Hz), 4.86 (d, 1H, J=12.0 Hz), 3.97 (s, 3H), 3.83 (m, 4H), 3.70 (br s, 4H), 3.45 (m, 2H), 3.37 (m, 2H), 3.17 (m, 1H). LCMS (ESI) m/z 705.43 (MNa+), 683.39 (MH+). 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-3edd05f06d294d3492afe059b3173096
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

Loading…