Methanol → 4-(7-sec-Butyl-5-cyano-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

HRID 2093637Notes

Reaction equation

HRID 2093637 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](/[C:38](/[CH3:41])=[CH:39]\[CH3:40])[C:6]2[O:10][C:9]([C:11]3[CH:36]=[CH:35][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][N:22]([C:25]5[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:37]=1)#[N:2].ClCCl.CO>C(OCC)(=O)C.[Pd]>[CH:38]([C:5]1[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:25]5[N:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:35][CH:36]=3)=[N:8][C:7]=2[CH:37]=[C:3]([C:1]#[N:2])[CH:4]=1)([CH2:39][CH3:40])[CH3:41]

Participants

6

Reactant 3

HCID 887MethanolHCID 6344DichloromethaneHCID 687875624-{5-Cyano-7-[(1Z)-1-methylprop-1-en-1-yl]-1,3-benzoxazol-2-yl}-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

Product 1

HCID 251724884-(7-sec-Butyl-5-cyano-1,3-benzoxazol-2-yl)-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 4-{5-cyano-7-[(1Z)-1-methylprop-1-en-1-yl]-1,3-benzoxazol-2-yl}-N-({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamide (18 mg) in ethyl acetate (5 ml)/dichloromethane (5 ml)/methanol (5 ml) at 40° C. was added 15 mg of 10% Pd/C and the resulting mixture was degassed and flushed with nitrogen, followed by degassing and flushing with hydrogen using a double balloon. The mixture was stirred under hydrogen at 40° C. overnight, and then filtered, washing with ethyl acetate. The filtrate was concentrated and purified by flash column chromatography on a Biotage Horizon, 25M Si column, eluting with 1 column volume of 10% ethyl acetate in hexanes, followed by a linear gradient of ethyl acetate in hexanes from 10% to 100% over 10 column volumes to afford the title compound. Mass spectrum (ESI) 563.2 (M+1). 1H NMR (500 MHz, CDCl3) δ: 8.47 (d, J=4.8 Hz, 1H), 8.34 (d, J=8.2 Hz, 2H), 7.95 (d, J=8.7 Hz, 2H), 7.49 (s, 1H), 6.73 (d, J=4.8 Hz, 1H), 6.32 (t, J=5.9 Hz, 1H), 4.87 (d, J=13.3 Hz, 2H), 3.44 (t, J=6.7 Hz, 2H), 3.21 (m, 1H), 2.93 (m, 2H), 2.01 (m, 1H), 1.90 (m, 2H), 1.84 (m, 2H), 1.44 (d, J=7.1 Hz, 3H), 1.31 (m, 2H), 0.91 (t, J=8.0 Hz, 3H).

Workup

  1. customthe resulting mixture was degassed
  2. customflushed with nitrogen
  3. customby degassing
  4. customflushing with hydrogen using a double balloon
  5. filtrationfiltered
  6. washwashing with ethyl acetate
  7. concentrationThe filtrate was concentrated
  8. custompurified by flash column chromatography on a Biotage Horizon, 25M Si column
  9. washeluting with 1 column volume of 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8d7e294da1154808b5a1a1ccc869527a
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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