Methyl chloroformate → Methyl 4-(6-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate

HRID 711260Notes

Reaction equation

HRID 711260 reaction equation
[F:1][C:2]1[C:3]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[N:4][CH:5]=[C:6]([CH2:8][NH:9][C:10](=[O:23])[C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][N:12]=2)[CH:7]=1.CCN(C(C)C)C(C)C.Cl[C:44]([O:46][CH3:47])=[O:45]>C1COCC1>[F:1][C:2]1[C:3]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:31])[F:32])[CH:25]=2)=[N:4][CH:5]=[C:6]([CH2:8][NH:9][C:10]([C:11]2[N:12]=[CH:13][C:14]([N:17]3[CH2:22][CH2:21][N:20]([C:44]([O:46][CH3:47])=[O:45])[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)=[O:23])[CH:7]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 68079457N-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methyl)-5-(piperazin-1-yl)picolinamide

Product 1

HCID 56599029Methyl 4-(6-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-((3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methyl)-5-(piperazin-1-yl)picolinamide 49-6 (64 mg, 0.14 mmol) and DIEA (0.07 mL, 0.42 mmol) in THF (1 mL) was added methyl chloroformate (13 uL, 0.17 mmol) dropwise at room temperature. The mixture was stirred for 2 hours. The solvent was removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give methyl 4-(6-((3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate 93 as a white powder. MS m/z 519.20 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 9.28 (t, 1H, J=6.4 Hz), 8.92 (d, 1H, J=5.2 Hz), 8.62 (m, 1H), 8.32 (m, 2H), 8.20 (d, 1H, J=5.2 Hz), 7.88-7.82 (m, 2H), 7.43 (dd, 1H, J1=7.0 Hz, J2=3.2 Hz), 4.59 (d, 2H, J=6.4 Hz), 3.73 (s, 3H), 3.54-3.51 (m, 4H), 3.37-3.35 (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-1f292641d9914a6fa44e326aaabdbe12
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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