Methanol → HCID 53373086, compound

HRID 515825Notes

Reaction equation

HRID 515825 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[O:6]=[C:7]1[C:11]2([CH2:14][CH2:13][CH2:12]2)[N:10]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:17][CH:16]=2)[C:9](=[S:28])[N:8]1[C:29]1[CH:30]=[C:31]([C:37]([F:40])([F:39])[F:38])[C:32]([C:35]#[N:36])=[N:33][CH:34]=1.C(N(CC)CC)C.CO>C1COCC1>[O:6]=[C:7]1[C:11]2([CH2:14][CH2:13][CH2:12]2)[N:10]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH:22]3[CH2:27][CH2:26][N:25]([C:1](=[O:4])[CH2:2][CH3:3])[CH2:24][CH2:23]3)=[CH:17][CH:16]=2)[C:9](=[S:28])[N:8]1[C:29]1[CH:30]=[C:31]([C:37]([F:39])([F:38])[F:40])[C:32]([C:35]#[N:36])=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 53373087HCID 53373087, compound

Product 1

HCID 53373086HCID 53373086, compoundYield 37.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Propionyl chloride (17 μL, 0.2 mmol) was added to 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 (50 mg, 0.1 mmol) and triethylamine (28 μL, 0.2 mmol) in THF (2 mL) and the resulting milky mixture was stirred at room temperature overnight. Methanol was added to quench the reaction and the mixture was absorbed on silica gel and purified by column chromatography on silica gel eluting with 50 to 100% EtOAc/hexanes to afford 21 mg of 5-(8-oxo-5-(4-((1-propionylpiperidin-4-yl)oxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.15 (d, 1H), 8.69 (s, 1H), 7.25 (d, 2H), 7.13 (d, 2H), 4.62 (m, 1H), 3.85 (m, 1H), 3.62 (m, 1H), 3.29 (m, 1H), 3.15 (m, 1H), 2.55-2.52 (m, 2H), 2.42 (m, 2H), 2.39-2.25 (m, 2H), 1.92-1.88 (m, 3H), 1.50-1.45 (m, 3H), 0.93 (t, 3H). LCMS [M+1]+ 558.1.

Workup

  1. customto quench
  2. customthe reaction
  3. customthe mixture was absorbed on silica gel
  4. custompurified by column chromatography on silica gel eluting with 50 to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-af00de5616224634a9683850793ccff6
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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