Acetic Anhydride → HCID 178473779, compound

HRID 2367799Notes

Reaction equation

HRID 2367799 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, 2.1 Hz), 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-bac9e4d782b84b5fb5bc4a57e42c410b
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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