Water → HCID 53372816, compound

HRID 515828Notes

Reaction equation

HRID 515828 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:9][CH2:8][CH2:7]2)[N:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)[C:4](=[S:23])[N:3]1[C:24]1[CH:25]=[C:26]([C:32]([F:35])([F:34])[F:33])[C:27]([C:30]#[N:31])=[N:28][CH:29]=1.[N:36]([Si](C)(C)C)=[C:37]=[O:38].O>C(Cl)Cl>[C:30]([C:27]1[N:28]=[CH:29][C:24]([N:3]2[C:2](=[O:1])[C:6]3([CH2:9][CH2:8][CH2:7]3)[N:5]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH:17]4[CH2:22][CH2:21][N:20]([C:37]([NH2:36])=[O:38])[CH2:19][CH2:18]4)=[CH:12][CH:11]=3)[C:4]2=[S:23])=[CH:25][C:26]=1[C:32]([F:34])([F:33])[F:35])#[N:31]

Participants

5

Reactant 3

HCID 962WaterHCID 70696Trimethylsilyl isocyanateHCID 53373087HCID 53373087, compound

Product 1

HCID 53372816HCID 53372816, compoundYield 72.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(8-oxo-5-(4-(piperidin-4-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (70 mg, 0.14 mmol) and isocyanatotrimethylsilane (23 μL, 0.17 mmol) in DCM (3 mL) was stirred at room temperature overnight. Water was added and the mixture was stirred vigorously for 1 h. The aqueous layer was extracted with DCM (3×), the organics were combined, dried over sodium sulfate, and evaporated to dryness. Column chromatography on silica gel (0 to 20% MeOH/DCM) afforded 55 mg of 4-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenoxy)piperidine-1-carboxamide as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.69 (s, 1H), 7.23 (d, 2H), 7.12 (d, 2H), 5.92 (s, 2H), 4.53 (m, 1H), 3.67-3.63 (m, 2H), 3.08-3.04 (m, 2H), 2.44 (m, 2H), 2.39 (m, 2H), 1.88 (m, 3H), 1.46 (m, 3H). LCMS [M+1]+ 545.2

Workup

  1. stirringthe mixture was stirred vigorously for 1 h
  2. extractionThe aqueous layer was extracted with DCM (3×)
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-7b0d37898a41415ba1e051a5ddc2aa49
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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