Diisopropylethylamine → 2-(4-(2-(difluoromethyl)pyridin-4-yl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide

HRID 592230Notes

Reaction equation

HRID 592230 reaction equation
[F:1][CH:2]([F:19])[C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]=1.[N:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[F:19][CH:2]([F:1])[C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[CH:11][C:12]([CH2:15][C:16]([NH:32][C:29]3[CH:28]=[CH:27][C:26]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][N:20]=4)=[CH:31][N:30]=3)=[O:18])=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584478202-(4-(2-(Difluoromethyl)pyridin-4-yl)phenyl)acetic acidHCID 592592255-(Pyrazin-2-yl)pyridin-2-amine

Product 1

HCID 584479052-(4-(2-(difluoromethyl)pyridin-4-yl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-(2-(difluoromethyl)pyridin-4-yl)phenyl)acetic acid 203-5 (70 mg, 0.27 mmol), 5-(pyrazin-2-yl)pyridin-2-amine (55 mg, 0.32 mmol), N,N-diisopropylethylamine (139 μL, 0.80 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (152 mg, 0.40 mmol) in DMF (2 mL) was stirred at room temperature overnight. The solvent was removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give 2-(4-(2-(difluoromethyl)pyridin-4-yl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide 203. MS m/z 418.2 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.99(d, 1H), 8.90(dd, 1H), 8.70(d, 1H), 8.63(dd, 1H), 8.53(d, 1H), 8.40-8.33(m, 2H), 8.30(s, 1H), 7.84(s, 1H), 7.70-7.68(m, 2H), 7.62-7.60(m, 1H), 7.50-7.49(m, 2H), 6.70(t, 1H), 3.87(s, 2H).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e437e92412d14e7b855e24a30c0b9bc8
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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