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

HRID 2093603Notes

Reaction equation

HRID 2093603 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:38]([CH3:40])[CH3:39])[C:6]2[O:10][C:9]([C:11]3[CH:36]=[CH:35][C:14]([C:15]([NH:17][CH2:18][C:19]4([CH:32]([CH3:34])[CH3:33])[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=O)[CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:37]=1)#[N:2].FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+].ClC1[N:60]=[C:59]([C:61]([F:64])([F:63])[F:62])[CH:58]=[CH:57][N:56]=1>ClCCl.CO>[C:1]([C:3]1[CH:4]=[C:5]([CH:38]([CH3:39])[CH3:40])[C:6]2[O:10][C:9]([C:11]3[CH:36]=[CH:35][C:14]([C:15]([NH:17][CH2:18][C:19]4([CH:32]([CH3:33])[CH3:34])[CH2:24][CH2:23][N:22]([C:25]5[N:60]=[C:59]([C:61]([F:64])([F:63])[F:62])[CH:58]=[CH:57][N:56]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:37]=1)#[N:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 25171653tert-Butyl 4-({[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}methyl)-4-isopropylpiperidine-1-carboxylate

Product 1

HCID 251716544-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-({4-isopropyl-1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)benzamideYield 87.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-({[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}methyl)-4-isopropylpiperidine-1-carboxylate (35 mg, 0.064 mmol) in dichloromethane was added trifluoroacetic acid. The mixture was stirred overnight at room temperature and then concentrated in vacuo. To the residue were added of methanol (2 ml), potassium carbonate (45 mg, 0.326 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (16 μl, 0.133 mmol). The mixture was heated to 50° C. and stirred at this temperature for 4 h, at which point LC/MS analysis showed a peak at the desired molecular weight. The reaction mixture was concentrated and then purified by flash chromatography on a Biotage Horizon, 25S column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes to provide the title compound (33 mg, 0.056 mmol, 87% yield). Mass spectrum (ESI) 591.1 (M+1). 1H NMR (500 MHz, CDCl3): 8.47 (d, J=4.5 Hz, 1H), 8.33 (d, J=8.5 Hz, 1H), 7.93 (s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.51 (s, 1H), 6.71 (d, J=5.0 Hz, 1H), 6.18 (br t, J=6.0 Hz, 1H), 4.18 (m, 2H), 3.65-3.75 (m, 4H), 3.47 (septet, J=7.0 Hz, 1H), 1.89 (septet, J=6.5 Hz, 1H), 1.70 (m, 2H), 1.50-1.60 (m, 2H), 1.46 (d, J=6.5 Hz, 6H), 1.02 (d, J=7.0 Hz, 6H).

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureThe mixture was heated to 50° C.
  3. stirringstirred at this temperature for 4 h, at which point LC/MS analysis
  4. concentrationThe reaction mixture was concentrated
  5. custompurified by flash chromatography on a Biotage Horizon, 25S column
  6. washeluting with 1 column volume of 100% dichloromethane

Sources & evidence

ORD record
ord-2c9b9297ae164cc6ab33798841b51210
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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