Isovaleryl chloride → HCID 22181317, compound

HRID 1796516Notes

Reaction equation

HRID 1796516 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([NH:14][CH3:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[CH:20][CH:19]=2)[CH3:17])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[C:36](Cl)(=[O:41])[CH2:37][CH:38]([CH3:40])[CH3:39]>CC#N.CN(C1C=CN=CC=1)C>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([N:14]([CH3:15])[C:36](=[O:41])[CH2:37][CH:38]([CH3:40])[CH3:39])=[CH:13][C:8]=3[N:7]=[C:6]2[CH:16]([C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH3:26])=[CH:22][CH:23]=2)[CH3:17])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 66054Isovaleryl chlorideHCID 81531DiisopropylethylamineHCID 22181285HCID 22181285, compound

Product 1

HCID 22181317HCID 22181317, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-(cyclopropylmethyl)-2-[1-(4-ethoxyphenyl)ethyl]-N-methyl-1H-benzimidazol-5-amine (349.5 mg, 1.0 mmol) in MeCN (25 mL) was added DIPEA (258.5 mg, 2.0 mmol), DMAP (10 mg) and isovaleryl chloride (180.9 mg, 1.5 mmol) at 0° C. The reaction mixture was stirred overnight at room temperature which was quenched with H2O (150 mL) and extracted with EtOAc (4×50 mL). The combined organic phases were washed with brine and dried with Na2SO4. Upon filtration and evaporation of the solvent, the residue was purified by MPLC using EtOAc on silica gel to give 431.9 mg (99%) of the desired product as a colorless syrup, which was converted to a TFA salt as a white solid. 1HNMR (400 MHz, CD3OD): δ 0.22 (m, 1H), 0.45 (m, 2H), 0.57 (m, 1H), 0.86 (d, J=5.9 Hz, 6H), 1.02 (m, 1H), 1.38 (t, J=7.0 Hz, 3H), 1.83 (d, J=7.0 Hz, 3H), 2.06 (m, 2H), 2.10 (m, 1H), 3.34 (s, 3H), 4.02 (m, 3H), 4.21 (dd, J=15.0, 6.6 Hz, 1H), 4.65 (q, J=7.0 Hz, 1H), 6.90 (d, J=8.6 Hz, 2H), 7.21 (d, J=8.6 Hz, 2H), 7.28 (d, J=8.4 Hz, 1H), 7.62 (s, 1H), 7.72 (d, J=8.6 Hz, 1H). MS (ESI) (M+H)+=434.42 (M+1)+. Anal: Calcd for C27H35N3O2+0.80TFA+0.90MeOH: C, 64.00; H, 7.17; N, 7.54. Found: C, 63.98; H, 7.02; N, 7.34.

Workup

  1. customwas quenched with H2O (150 mL)
  2. extractionextracted with EtOAc (4×50 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationUpon filtration and evaporation of the solvent
  6. customthe residue was purified by MPLC

Sources & evidence

ORD record
ord-1f1919e7119841eea0d6548cfdf6af38
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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