Acetyl chloride → HCID 178474717, compound

HRID 1190086Notes

Reaction equation

HRID 1190086 reaction equation
[C:1](O)(=[O:3])[CH3:2].[NH2:5][C:6]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[NH:19][CH:20]=[C:21]([C:23]#[N:24])[N:22]=2)=[O:17])=[C:11]([C:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]=2)[CH:10]=1)([CH3:8])[CH3:7].CCN(C(C)C)C(C)C.CN(C1C=CC=CN=1)C.C(Cl)(=O)C>C(Cl)(Cl)Cl.CCOC(C)=O>[C:1]([NH:5][C:6]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[NH:19][CH:20]=[C:21]([C:23]#[N:24])[N:22]=2)=[O:17])=[C:11]([C:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]=2)[CH:10]=1)([CH3:8])[CH3:7])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 178476304HCID 178476304, compound

Product 1

HCID 178474717HCID 178474717, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-cyano-1H-imidazole-2-carboxylic acid [4-(1-amino-1-methyl-ethyl)-2-cyclohex-1-enyl-phenyl]-amide acetic acid salt (as prepared in the previous step, 50.0 mg, 0.122 mmol) and DIEA (85.0 μL, 0.488 mmol) in 2 mL of CHCl3 was stirred at RT for 5 min before dimethylaminopyridine (DMAP) (4.1 mg, 0.037 mmol) was added. The mixture was cooled to 0° C. and a solution of acetyl chloride (10 μL, 0.15 mmol) in 2 mL of CHCl3 was added dropwise. The reaction was warmed to RT and stirred for 18 h under Ar. The mixture was treated with EtOAc (40 mL), washed with saturated aqueous NaHCO3 (5 mL), brine (10 mL) and dried over Na2SO4. Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-2% MeOH/DCM) gave 7.6 mg (16%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.17 (s, 1H), 8.10 (d, 1H, J=8.6 Hz), 7.99 (s, 1H), 7.27 (dd, 1H, J=8.6, 2.3 Hz), 7.16 (d, 1H, J=2.3 Hz), 5.80 (m, 1H), 2.20-2.32 (m, 4H), 1.94 (s, 3H), 1.74-1.88 (m, 4H), 1.62 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C22H25N5O2, 392.2 (M+H). found 391.8.

Workup

  1. additionwas added
  2. temperatureThe reaction was warmed to RT
  3. washwashed with saturated aqueous NaHCO3 (5 mL), brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-a9b5f463741645428c339182add45854
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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