Hydrochloric Acid → HCID 44226868, compound

HRID 390160Notes

Reaction equation

HRID 390160 reaction equation
Cl.[N:2]1([C:17](=[O:30])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]([F:29])([F:28])[F:27])[CH2:7][CH2:6][C:5]2([C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10][NH:9][CH2:8]2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42].Cl>C(Cl)Cl>[CH3:40][S:41]([N:9]1[CH2:8][C:5]2([CH2:6][CH2:7][N:2]([C:17](=[O:30])/[CH:18]=[CH:19]/[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:28])([F:27])[F:29])[CH2:3][CH2:4]2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10]1)(=[O:43])=[O:42]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67223828HCID 67223828, compound

Product 1

HCID 44226868HCID 44226868, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (E)-1-(2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one HCl salt (40 mg, 0.09 mmol) in CH2Cl2 (4 mL) was treated with i-Pr2NEt (0.05 mL, 0.28 mmol) and MeSO2Cl (0.014 mL, 0.18 mmol). The mixture was stirred overnight at rt and applied to a 10-mL Chem-Elut cartridge that had been wetted with 5% aq HCl (6 mL). The cartridge was eluted with ether (20 mL). The eluate was concentrated and the residue was purified by prep HPLC to afford (E)-1-(2-(methylsulfonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one (20 mg, 45%). 1H NMR (CDCl3) 1.77 (m, 1H), 1.88 (m, 1H), 2.04 (m, 1H), 2.13 (m, 1H), 2.92 (s, 3H), 3.00 (m, 1H), 3.23 (m, 1H), 3.47 (m, 1H), 3.90 (m, 1H), 4.02 (m, 1H), 4.37 (m, 1H), 4.59 (m, 1H), 4.78 (d, 1H), 6.82 (d, 1H), 7.05-7.75 (8H), 7.99 (d, 1H).

Workup

  1. washThe cartridge was eluted with ether (20 mL)
  2. concentrationThe eluate was concentrated
  3. customthe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-03cca27c371b43b08a57894fbe6f5da4
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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