2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 118062853, compound

HRID 920815Notes

Reaction equation

HRID 920815 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=4)[C:16]([C:17]([NH2:19])=[O:18])=[C:10]3[CH2:9]2)=[O:7])[CH2:2]1.CCN(C(C)C)C(C)C.FC(F)(F)S(O[CH2:43][C:44]([F:47])([F:46])[F:45])(=O)=O>C1COCC1>[Cl:27][C:22]1[CH:21]=[C:20]([C:15]2[C:16]([C:17]([NH2:19])=[O:18])=[C:10]3[CH2:9][N:8]([C:6]([NH:5][CH:3]4[CH2:2][N:1]([CH2:43][C:44]([F:47])([F:46])[F:45])[CH2:4]4)=[O:7])[CH2:13][CH2:12][N:11]3[N:14]=2)[CH:25]=[CH:24][C:23]=1[F:26]

Participants

5

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 81531DiisopropylethylamineHCID 118071095HCID 118071095, compound

Product 1

HCID 118062853HCID 118062853, compoundYield 12.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of Intermediate 339B (100 mg, 0.255 mmol) in THF (10 mL) was added DIPEA (0.222 mL, 1.273 mmol) followed by 2,2,2-trifluoroethyl trifluoromethanesulfonate (118 mg, 0.509 mmol) and stirred at RT for 16 h. The reaction mixture was quenched with a 10% aqueous solution of NaHCO3 and extracted with EtOAc (2×20 mL) The combined organic layer was dried over Na2SO4, filtered and the filtrate evaporated. The crude compound was purified by preparative HPLC to afford Compound 339 as an off-white solid (15 mg, 12%). HPLC retention times 10.73 min. and 11.90 min (Methods C and D). MS(ES): m/z=475 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.84 (dd, J=7.37, 2.08 Hz, 1H), 7.62-7.72 (m, 1H), 7.41-7.50 (m, 1H), 7.36 (br. s., 1H), 7.27 (d, J=6.80 Hz, 1H), 7.18 (br. s., 1H), 4.73 (s, 2H) 4.19-4.31 (m, 1H), 4.06-4.17 (m, 2H), 3.84 (d, J=5.67 Hz, 2H), 3.57-3.69 (m, 2H), 3.09-3.23 (m, 4H).

Workup

  1. customThe reaction mixture was quenched with a 10% aqueous solution of NaHCO3
  2. extractionextracted with EtOAc (2×20 mL) The combined organic layer
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. customthe filtrate evaporated
  6. customThe crude compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-f7adf29dc26744709a30cd98b93facbb
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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