Acetic Anhydride → 5-(5-(4-(2-(4-Acetylpiperazin-1-yl)ethoxy)-3-fluorophenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile

HRID 515821Notes

Reaction equation

HRID 515821 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:17]2[C:24](=[S:25])[N:23]([C:26]3[CH:27]=[C:28]([C:34]([F:37])([F:36])[F:35])[C:29]([C:32]#[N:33])=[N:30][CH:31]=3)[C:22](=[O:38])[C:18]32[CH2:21][CH2:20][CH2:19]3)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[C:39](OC(=O)C)(=[O:41])[CH3:40].C(N(CC)CC)C>C(Cl)Cl>[C:39]([N:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][O:8][C:7]2[CH:6]=[CH:5][C:4]([N:17]3[C:24](=[S:25])[N:23]([C:26]4[CH:27]=[C:28]([C:34]([F:36])([F:37])[F:35])[C:29]([C:32]#[N:33])=[N:30][CH:31]=4)[C:22](=[O:38])[C:18]43[CH2:19][CH2:20][CH2:21]4)=[CH:3][C:2]=2[F:1])[CH2:12][CH2:13]1)(=[O:41])[CH3:40]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 866834845-(5-(3-Fluoro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile2×

Product 1

HCID 533732215-(5-(4-(2-(4-Acetylpiperazin-1-yl)ethoxy)-3-fluorophenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrileYield 57.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(5-(3-fluoro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (Compound 174, 50 mg, 0.1 mmol), acetic anhydride (13 μL, 0.14 mmol), and triethylamine (40 μL, 0.27 mmol) in DCM (2 mL) was stirred at room temperature for 2 days. The reaction mixture was absorbed on silica gel and purified by column chromatography on silica gel eluting with 0 to 10% MeOH/DCM to afford 34 mg of 5-(5-(4-(2-(4-acetylpiperazin-1-yl)ethoxy)-3-fluorophenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.74 (s, 1H), 7.42 (t, 1H), 7.35 (dd, 1H), 7.22 (m, 1H), 4.28 (t, 2H), 3.42 (m, 4H), 2.80 (t, 2H), 2.65-2.59 (m, 2H), 2.54-2.44 (m, 6H), 1.98 (m, 4H), 1.57 (m, 1H). LCMS [M+1]+ 591.9.

Workup

  1. customThe reaction mixture was absorbed on silica gel
  2. custompurified by column chromatography on silica gel eluting with 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-726aa4e0067141e0a61327049c5d63da
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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