Trimethylsilyl isocyanate → HCID 86690654, compound

HRID 1505621Notes

Reaction equation

HRID 1505621 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[CH2:15][N:16]([CH2:27][C:28]([F:31])([F:30])[F:29])[S:17]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:19])=[O:18].C(N(CC)C(C)C)(C)C.[N:41]([Si](C)(C)C)=[C:42]=[O:43].C([O-])(O)=O.[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[F:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C:42]([NH2:41])=[O:43])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[CH2:15][N:16]([CH2:27][C:28]([F:31])([F:29])[F:30])[S:17]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:19])=[O:18]

Participants

7

Reactant 4

HCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 86690650HCID 86690650, compound

Product 1

HCID 86690654HCID 86690654, compoundYield 13.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-[[2-fluoro-4-(4-piperidyl)phenyl]methyl]-1-phenyl-N-(2,2,2-trifluoroethyl)methanesulfonamide hydrochloride (Example 7, Step 2), (200 mg, 0.41 mmol) and N,N-diisopropylethylamine (0.36 mL, 2.0 mmol) in dichloromethane (4 mL) was added 4-dimethylaminopyridine (5 mg, 0.041 mmol), followed by isocyanato(trimethyl)silane (0.30 mL, 2.1 mmol) and the reaction was stirred at ambient temperature for 2 hours. Saturated aqueous NaHCO3 was then added and the dichloromethane layer was isolated with a phase-separator cartridge. The organic layer was concentrated and purified by preparative reverse phase HPLC to yield 27 mg of 4-(3-fluoro-4-((1-phenyl-N-(2,2,2-trifluoroethyl)methylsulfonamido)methyl)phenyl)piperidine-1-carboxamide. 1H NMR (400 MHz, DMSO) δ 7.44-7.38 (m, 5H), 7.38-7.29 (m, 1H), 7.16-7.02 (m, 2H), 5.88 (s, 2H), 4.59 (s, 2H), 4.41 (s, 2H), 4.13-4.00 (m, 2H), 3.95 (q, J=9.3 Hz, 2H), 2.82-2.61 (m, 3H), 1.80-1.64 (m, 2H), 1.56-1.32 (m, 2H); LCMS (m/z) ES+ 488.1 [M+1]+.

Workup

  1. concentrationThe organic layer was concentrated
  2. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-c1ffc25531e049199ac9b7d6788e89ed
Source dataset
uspto-grants-2015_12
Patent number
US09216988B2

Reaction notes

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