Water → HCID 178424469, compound

HRID 536938Notes

Reaction equation

HRID 536938 reaction equation
C[O:2][C:3]([C:5]1([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[NH:21][CH:22]=[C:23]([C:25]#[N:26])[N:24]=3)=[O:19])=[C:13]([C:27]3[CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH2:29][CH:28]=3)[CH:12]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].[OH-].[Na+].O>C1COCC1.CO>[C:25]([C:23]1[N:24]=[C:20]([C:18]([NH:17][C:14]2[CH:15]=[CH:16][C:11]([C:5]3([C:3]([OH:4])=[O:2])[CH2:6][CH2:7][O:8][CH2:9][CH2:10]3)=[CH:12][C:13]=2[C:27]2[CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH2:29][CH:28]=2)=[O:19])[NH:21][CH:22]=1)#[N:26]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 178496846HCID 178496846, compound

Product 1

HCID 178424469HCID 178424469, compoundYield 95.1%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 4-[4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-tetrahydro-pyran-4-carboxylic acid methyl ester (as prepared in Example 16, step (f), 129 mg, 0.279 mmol) in 2 mL of 1:1 THF/MeOH was added 6 N NaOH (400 μL, 2.40 mmol). After stirring at RT for 2 d, the mixture was treated with 10 mL of H2O and washed with EtOAc (3×10 mL). The aqueous layer was acidified to pH=5 with 15% citric acid and extracted with 10:1 EtOAc-MeOH (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo to afford 119 mg (95%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.20 (d, 1H, J=8.8 Hz), 8.00 (s, 1H), 7.37 (dd, 1H, J=8.8, 2.3 Hz), 7.24 (d, 1H, J=2.3 Hz), 5.75 (m, 1H), 3.91 (m, 2H), 3.61 (t, 2H, J=11.5 Hz), 2.49 (m, 2H), 2.30 (m, 2H), 2.08 (m, 2H), 1.95 (m, 2H), 1.60 (t, 2H, J=6.1 Hz), 1.09 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H28N4O4, 449.2 (M+H). found 449.2.

Workup

  1. washwashed with EtOAc (3×10 mL)
  2. extractionextracted with 10:1 EtOAc-MeOH (3×10 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-615b37ab34754ada8c4adbbaf2c0da1d
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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