Diethyl Pyrocarbonate → 1-[(4-fluorophenyl)sulfonylamino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

HRID 1479856Notes

Reaction equation

HRID 1479856 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2([C:15]([OH:17])=O)[CH2:14][CH2:13]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCOC(OC(OCC)=O)=O.[N:29]1([C:34]2[CH:39]=[C:38]([CH2:40][NH2:41])[CH:37]=[C:36]([C:42]3[CH:47]=[CH:46][C:45]([O:48][C:49]([F:52])([F:51])[F:50])=[CH:44][CH:43]=3)[N:35]=2)[CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:12]2([C:15]([NH:41][CH2:40][C:38]3[CH:37]=[C:36]([C:42]4[CH:43]=[CH:44][C:45]([O:48][C:49]([F:52])([F:50])[F:51])=[CH:46][CH:47]=4)[N:35]=[C:34]([N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:39]=3)=[O:17])[CH2:13][CH2:14]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 607292541-[(4-Fluorophenyl)sulfonylamino]cyclopropanecarboxylic acidHCID 131736589[2-Pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine

Product 1

HCID 903841731-[(4-fluorophenyl)sulfonylamino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acid 15C (260 mg, 1 mmol) was dissolved in 5 ml of THF and at rt DEPC (1.1 equiv, 0.17 ml) and [2-pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine 27C (1.1 equiv., 371 mg) were added to the solution. The mixture was stirred at rt overnight then evaporated. The residue was dissolved in EtOAc (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude by chromatographic column (3:7 EtOAc:Petroleum ether) afforded 130 mg of a white solid. Yield=22% 1HNMR (DMSO, 200 MHz) δ 0.71 (2H, bm), 1.08 (2H, bm), 1.92 (4H, m), 3.47 (4H, m), 4.29 (2H, d, J=5.6 Hz), 6.41 (1H, s), 7.09 (1H, s), 7.45 (4H, m), 7.82 (2H, m), 8.17 (2H, d, J=9 Hz), 8.38 (1H, t), 8.71 (1H, bs) [M+1] 579.4 (C27H26F4N4O4S requires 578.58).

Workup

  1. additionwere added to the solution
  2. customthen evaporated
  3. dissolutionThe residue was dissolved in EtOAc (30 ml)
  4. washwashed with water (1×20 ml) and brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe purification of the crude by chromatographic column (3:7 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-3243b1291ad445858832473beedca6a0
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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