Diisopropylethylamine → HCID 25171034, compound

HRID 2093594Notes

Reaction equation

HRID 2093594 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:28]([CH3:30])[CH3:29])[C:6]2[O:10][C:9]([C:11]3[CH:26]=[CH:25][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:27]=1)#[N:2].[CH:31]1([CH2:37][CH2:38][C:39](Cl)=[O:40])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.C(N(C(C)C)CC)(C)C>ClCCl.C(OCC)(=O)C.O>[C:1]([C:3]1[CH:4]=[C:5]([CH:28]([CH3:30])[CH3:29])[C:6]2[O:10][C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][N:22]([C:39](=[O:40])[CH2:38][CH2:37][CH:31]5[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]5)[CH2:21][CH2:20]4)=[O:16])=[CH:25][CH:26]=3)=[N:8][C:7]=2[CH:27]=1)#[N:2]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734098Cyclohexylpropionyl chlorideHCID 68745687HCID 68745687, compound2×

Product 1

HCID 25171034HCID 25171034, compoundYield 44.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (20 mg, INTERMEDIATE 15) in 5 ml of dichloromethane was added 3-cyclohexylpropanoyl chloride (13 mg), and then diisopropylethylamine (450 μl). The reaction was stirred for 2 h at room temperature. The mixture was then diluted with 10 ml of ethyl acetate and 10 ml of water. The phases were separated and the aqueous phase was extracted with 10 ml of ethyl acetate. The combined organic phases were washed with 10 ml of brine, dried over Na2SO4, and concentrated. The residue was purified by reverse-phase HPLC on a Biotage Parallex Flex, Kromasil C18 21×100 mm column, eluting at 15 ml/min with 90% water (0.1% TFA) to 95% acetonitrile (0.1% TFA) over 10 min, hold for 2 min, then back to 90% water over 0.5 min, hold for 0.5 min, to provide the title compound (12 mg, 36%). Mass spectrum (ESI) 541.3 (M+1). 1H NMR signals are doubled and broadened because of restricted rotation about the amide C—N bond. 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8 Hz, 2H), 8.19 (s, 1H), 7.95 (d, J=8 Hz, 2H), 7.92 (d, J=1 Hz, 1H), 7.51 (s, 1H), 6.68-6.70 (m, 1H), 6.65 (m, 1H), 3.89-3.98 (m, 1H), 3.44-3.50 (m, 2H), 3.35 (m, 1H), 3.084 (m, 1H), 2.72 (s, 1H), 2.62 (m, 1H), 2.37-2.40 (m, 3H), 1.98 (m, 1H), 1.87 (m, 2H), 1.62-1.70 (m, 7H), 1.48 (m, 3H), 1.45 (d, J=7 Hz, 6H), 1.336 (d, H=7 Hz, 2H), 1.09-1.24 (m, 10H), 0.86-0.93 (m, 3H).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with 10 ml of ethyl acetate
  3. washThe combined organic phases were washed with 10 ml of brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase HPLC on a Biotage Parallex Flex, Kromasil C18 21×100 mm column
  7. washeluting at 15 ml/min with 90% water (0.1% TFA) to 95% acetonitrile (0.1% TFA) over 10 min
  8. waithold for 2 min
  9. waitback to 90% water over 0.5 min
  10. waithold for 0.5 min

Sources & evidence

ORD record
ord-86a999b82ce247049eefde05a808dd61
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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