Acetic Anhydride → HCID 178473779, compound

HRID 1991977Notes

Reaction equation

HRID 1991977 reaction equation
F[C:2](F)(F)[C:3](O)=[O:4].[O:8]=[S:9]1(=[O:37])[CH2:14][CH:13]=[C:12]([C:15]2[CH:20]=[C:19]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:28]([C:30]2[NH:31][CH:32]=[C:33]([C:35]#[N:36])[N:34]=2)=[O:29])[CH2:11][CH2:10]1.CCN(C(C)C)C(C)C.C(OC(=O)C)(=O)C.CCOC(C)=O>C(Cl)Cl.CN(C=O)C>[C:3]([N:24]1[CH2:25][CH2:26][CH:21]([C:19]2[CH:18]=[CH:17][C:16]([NH:27][C:28]([C:30]3[NH:31][CH:32]=[C:33]([C:35]#[N:36])[N:34]=3)=[O:29])=[C:15]([C:12]3[CH2:13][CH2:14][S:9](=[O:8])(=[O:37])[CH2:10][CH:11]=3)[CH:20]=2)[CH2:22][CH2:23]1)(=[O:4])[CH3:2]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 178510385HCID 178510385, compound

Product 1

HCID 178473779HCID 178473779, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a suspension of 4-cyano-1H-imidazole-2-carboxylic acid [2-(1,1-dioxo-1,2,3,6-tetrahydro-1λ6-thiopyran-4-yl)-4-piperidin-4-yl-phenyl]-amide trifluoroacetic acid salt (as prepared in Example 36, step (e), 62 mg, 0.115 mmol) in 4 mL of 1:1 DCM/DMF at RT was added DIEA (60 μL, 0.345 mmol). The mixture was stirred for 5 min, then acetic anhydride (11 μL, 0.121 mmol) was added slowly to the mixture, and the resulting mixture was stirred at RT for 0.5 h. Treated with 40 mL of EtOAc, the mixture was washed with H2O (2×20 mL). The aqueous layers were extracted with EtOAc (4×10 mL). The combined organic layers were concentrated in vacuo. The residue was purified by flash chromatography on silica gel (1-4% MeOH/DCM) yielding 50.9 mg (95%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 13.0 (s, 1H), 9.10 (s, 1H), 8.13 (d, 1H, J=8.4 Hz), 7.77 (d, 1H, J=2.3 Hz), 7.26 (dd, 1H, J=8.4, 2.0 Hz), 7.08 (d, 1H, J=2.0 Hz), 5.77 (t, 1H, J=4.3 Hz), 4.84 (dt, 1H, J=13.3, 2.1Hz), 4.00 (dt, 1H, J=13.3, 2.1 Hz), 3.89 (br s, 2H), 3.31 (t, 2H, J=6.2 Hz), 3.23 (td, 1H, J=13.2, 2.5 Hz), 3.02 (m, 2H), 2.77 (dddd, 1H, J=11.9, 11.9, 3.4, 3.4 Hz), 2.68 (ddd, 1H, J=12.6, 12.6, 2.9 Hz), 2.18 (s, 3H), 1.70-1.97 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C23H25N5O4S, 468.2 (M+H), found 468.1.

Workup

  1. stirringthe resulting mixture was stirred at RT for 0.5 h
  2. washthe mixture was washed with H2O (2×20 mL)
  3. extractionThe aqueous layers were extracted with EtOAc (4×10 mL)
  4. concentrationThe combined organic layers were concentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (1-4% MeOH/DCM)

Sources & evidence

ORD record
ord-8dc1f47553774d41a9e8bec309d2a729
Source dataset
uspto-grants-2010_01
Patent number
US07645755B2

Reaction notes

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