Ethyl Acetate → N-(4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)-2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

HRID 1050162Notes

Reaction equation

HRID 1050162 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](O)=[O:28])=[C:22]([F:30])[CH:21]=1)[CH3:2].[Br:31][C:32]1[CH:37]=[C:36]([C:38]([CH3:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])[N:35]=[CH:34][C:33]=1[NH2:45].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CC(=O)OCC>N1C=CC=CC=1>[Br:31][C:32]1[CH:37]=[C:36]([C:38]([CH3:43])([CH3:44])[C:39]([F:40])([F:41])[F:42])[N:35]=[CH:34][C:33]=1[NH:45][C:27](=[O:28])[CH2:26][C:23]1[CH:24]=[CH:25][C:20]([C:5]2[CH:6]=[N:7][C:8]([O:10][CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)=[CH:9][C:4]=2[O:3][CH2:1][CH3:2])=[CH:21][C:22]=1[F:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 904227052-(4-(4-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acidHCID 904233454-Bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-amine

Product 1

HCID 90423574N-(4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)-2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamideYield 52.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (30 mg, 0.073 mmol) in pyridine (5 mL) was added 4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-amine (20.64 mg, 0.073 mmol) and T3P® (EA solvate) (0.5 mL, 0.073 mmol). The mixture was stirred at 25° C. for 1 h. The mixture was concentrated and purified by preparative TLC (DCM/MeOH=15:1, Rf=0.6) to yield a light yellow solid of N-(4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)-2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (30 mg, 0.038 mmol, 51.7% yield): 1H NMR (400 MHz, CD3OD): δ 8.84 (s, 1H), 7.99 (s, 1H), 7.90 (s, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.40 (d, J=8.4 Hz, 2H), 7.33 (d, J=9.6 Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 6.48 (s, 1H), 5.30 (s, 2H), 4.16 (q, J=6.8 Hz, 2H), 3.93 (s, 2H), 3.82 (s, 3H), 1.63 (s, 6H), 1.40 (t, J=7.0 Hz, 3H). ES-LCMS m/z 678.0 (M+H+2).

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative TLC (DCM/MeOH=15:1, Rf=0.6)

Sources & evidence

ORD record
ord-1e8c6a5f3e964d8db0ec4ba0a06849f1
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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