Propylphosphonic anhydride → 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamide

HRID 1050168Notes

Reaction equation

HRID 1050168 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=O)=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[O:31]1[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][O:39][C:40]2[CH:41]=[C:42]([CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=2)[NH2:43])[CH2:33][CH2:32]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>N1C=CC=CC=1.CC(=O)OCC>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:43][C:42]3[CH:44]=[C:45]([C:47]([F:49])([F:50])[F:48])[CH:46]=[C:40]([O:39][CH2:38][CH2:37][N:34]4[CH2:33][CH2:32][O:31][CH2:36][CH2:35]4)[CH:41]=3)=[O:29])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2]

Participants

6

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 210495503-(2-Morpholinoethoxy)-5-(trifluoromethyl)anilineHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acid

Product 1

HCID 904233572-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamideYield 64.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (70.9 mg, 0.172 mmol) and 3-(2-morpholinoethoxy)-5-(trifluoromethyl)aniline (50 mg, 0.172 mmol) in pyridine (5 mL) was added T3P® (50% in EA, 0.3 mL) dropwise and the mixture was stirred at 25° C. for 1 h. The mixture was quenched with cold water (20 mL), extracted with DCM/MeOH (10:1, v/v, 20 mL×3). The organic layer was dried over Na2SO4 and concentrated to give an off white solid of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(3-(2-morpholinoethoxy)-5-(trifluoromethyl)phenyl)acetamide (80 mg, 0.111 mmol, 64.5% yield): 1H NMR (400 MHz, CD3OD): δ 7.94 (d, J=1.8 Hz, 1H), 7.54 (s, 1H), 7.48 (s, 1H), 7.45-7.35 (m, 6H), 6.95-6.88 (m, 3H), 5.35 (s, 2H), 4.20-4.10 (m, 4H), 3.80 (s, 2H), 3.78 (s, 3H), 3.73-3.66 (m, 4H), 2.81 (t, J=5.4 Hz, 2H), 2.59 (d, J=4.2 Hz, 4H), 1.41 (t, J=6.8 Hz, 3H). ES-LCMS m/z: 684 (M+H).

Workup

  1. customThe mixture was quenched with cold water (20 mL)
  2. extractionextracted with DCM/MeOH (10:1, v/v, 20 mL×3)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-25718d73fd42426bb3ea0ca0504eb0cc
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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