Triethylamine → HCID 25211499, compound

HRID 572294Notes

Reaction equation

HRID 572294 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([C:11]2[S:12][C:13]([C:16]3[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=3)=[CH:14][CH:15]=2)=[O:10])[CH2:4]1.C(N(CC)CC)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>C1COCC1>[CH3:21][C:20]1[C:16]([C:13]2[S:12][C:11]([C:9]([N:5]3[CH2:6][CH2:7][CH2:8][C@@H:3]([NH:2][S:34]([CH3:33])(=[O:36])=[O:35])[CH2:4]3)=[O:10])=[CH:15][CH:14]=2)=[N:17][O:18][C:19]=1[C:22]([F:25])([F:24])[F:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 131729821HCID 131729821, compound

Product 1

HCID 25211499HCID 25211499, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of ((R)-3-Amino-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochloride (Example 27, 79 mg, 0.2 mmol) in THF (2 mL) was treated with triethylamine (63 μL, 0.45 mmol) followed by methanesulfonyl chloride (19 μL, 0.24 mmol). The reaction mixture was allowed to stir 48 h, evaporated, and chromatographed on silica gel with EtOAc as eluant to afford product as a colorless foam (61 mg, 70%). 1H NMR (CDCl3) 1.68 (m, 2H), 1.88 (m, 2H), 2.02 (m, 1H), 2.33 (d, J=1.8, 3H), 2.98 (s, 3H), 3.46 (m, 2H), 3.57 (m, 1H), 3.84 (m, 1H), 4.05 (d, J=12.7, 1H), 5.45 (d, J=7.5, 1H), 7.39 (d, J=4.0, 1H), 7.43 (d, J=3.5, 1H). 13C NMR 7.9, 23.4, 31.6, 41.9, 47 (br), 52 (br), 49.9, 114.8, 118.7 (q, J=271), 128.2, 129.8, 131.8, 139.6, 155.2 (q, 40), 157.9, 163.5. 19F NMR −63.1. LC/MS 5.82 min, [M+1]+ 438.

Workup

  1. customevaporated
  2. customchromatographed on silica gel with EtOAc as eluant

Sources & evidence

ORD record
ord-d328e20b975c443eb58c73458cfbedcf
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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