Diethyl Pyrocarbonate → HCID 90390561, compound

HRID 1479889Notes

Reaction equation

HRID 1479889 reaction equation
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[CH:30]1([CH2:33][N:34]2[CH2:39][CH2:38][N:37]([C:40]3[CH:45]=[C:44]([CH2:46][NH2:47])[CH:43]=[C:42]([C:48]4[CH:53]=[CH:52][C:51]([O:54][C:55]([F:58])([F:57])[F:56])=[CH:50][CH:49]=4)[N:41]=3)[CH2:36][CH2:35]2)[CH2:32][CH2:31]1>C1COCC1>[CH:30]1([CH2:33][N:34]2[CH2:35][CH2:36][N:37]([C:40]3[CH:45]=[C:44]([CH2:46][NH:47][C:5](=[O:7])[C:4]([N:3]([CH2:1][CH3:2])[S:9]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)(=[O:11])=[O:10])=[CH2:8])[CH:43]=[C:42]([C:48]4[CH:53]=[CH:52][C:51]([O:54][C:55]([F:56])([F:58])[F:57])=[CH:50][CH:49]=4)[N:41]=3)[CH2:38][CH2:39]2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acidHCID 131736602HCID 131736602, compound

Product 1

HCID 90390561HCID 90390561, compoundYield 30.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4B (273.28 mg, 1 mmol) in THF (10 mL) was added with DEPC (0.15 mL, 1.1 mol eq) and the mixture was stirred at room temperature for about 5 minutes. Then [2-[4-(cyclopropylmethyl)piperazin-1-yl]-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine 27F (405 mg, 1.04 mol eq) and a catalytic amount of TEA were added, then the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was suspended in EtOAc (40 mL) and washed with water (50 mL) and brine. The separated organic phase was dried over Na2SO4 and evaporated under reduced pressure and the residue was purified by flash chromatography (9:1 EtOAc:methanol) to afford a white solid (200 mg) after crystallization from diethyl ether. Yield=30%, 1HNMR (DMSO, 200 MHz) δ 0.05 (m, 2H), 0.45 (bm, 2H), 0.82 (m, 1H), 1.08 (t, 3H), 2.17 (d, 2H, J=6.4), 3.34 (bm, 4H), 3.49 (bm, 4H), 4.43 (d, 2H, J=6.2), 5.13 (s, 1H); 6.09 (s, 1H), 6.80 (s, 1H), 7.30 (s, 1H), 7.47 (m, 4H), 7.85 (m, 4H), 8.74 (t, 1H). [M+1] 662.90 (C32H35F4N5O4S requires 661.71).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water (50 mL) and brine
  4. dry with materialThe separated organic phase was dried over Na2SO4
  5. customevaporated under reduced pressure
  6. customthe residue was purified by flash chromatography (9:1 EtOAc:methanol)

Sources & evidence

ORD record
ord-5ae151e19d724891a79a39075d7c976e
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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