Sodium hydride → HCID 25171238, compound

HRID 2093595Notes

Reaction equation

HRID 2093595 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].[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=1>O1CCCC1>[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]([CH2:34][C:35]5[CH:36]=[CH:37][C:38]([C:41]([F:42])([F:43])[F:44])=[CH:39][CH:40]=5)[CH2:21][CH2:20]4)=[O:16])=[CH:25][CH:26]=3)=[N:8][C:7]=2[CH:27]=1)#[N:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 68745687HCID 68745687, compound2×

Product 1

HCID 25171238HCID 25171238, compoundYield 14.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (25 mg, INTERMEDIATE 15) in tetrahydrofuran (5 ml) was added sodium hydride (5 mg of a 60% dispersion in oil). The reaction was allowed to stir at room temperature for five min, and then 1-(bromomethyl)-4-(trifluoromethyl)benzene was added. The reaction was stirred for 1 h and then was 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 (5 mg, 14.4%). Mass spectrum (ESI) 561.2 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.31 (d, J=8.5 Hz, 2H), 7.92-7.94 (m, 3H), 7.55 (d, J=8 Hz, 2H), 7.50 (s, 1H), 7.42 (d, J=8 Hz, 2H), 6.37 (m, 1H), 3.54 (s, 2H), 3.44-3.51 (m, 2H), 3.40 (m, 2H), 2.89 (m, 2H), 1.98-2.03 (m, 2H), 1.83 (s, 1H) 1.74-1.77 (m, 2H), 1.67-1.71 (m, 1H), 1.45 (d, J=7 Hz, 6H), 1.36-1.40 (m, 2H), 1.25 (m, 1H).

Workup

  1. stirringThe reaction was stirred for 1 h
  2. concentrationwas concentrated
  3. customThe residue was purified by reverse-phase HPLC on a Biotage Parallex Flex, Kromasil C18 21×100 mm column
  4. washeluting at 15 ml/min with 90% water (0.1% TFA) to 95% acetonitrile (0.1% TFA) over 10 min
  5. waithold for 2 min
  6. waitback to 90% water over 0.5 min
  7. waithold for 0.5 min

Sources & evidence

ORD record
ord-0d36f133b3a44992a8c076100fc8acf4
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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