Benzyl isocyanate → HCID 25171446, compound

HRID 2093597Notes

Reaction equation

HRID 2093597 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].[CH2:31]([N:38]=[C:39]=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl>[CH2:31]([NH:38][C:39]([N:22]1[CH2:23][CH2:24][CH:19]([CH2:18][NH:17][C:15](=[O:16])[C:14]2[CH:13]=[CH:12][C:11]([C:9]3[O:10][C:6]4[C:5]([CH:28]([CH3:30])[CH3:29])=[CH:4][C:3]([C:1]#[N:2])=[CH:27][C:7]=4[N:8]=3)=[CH:26][CH:25]=2)[CH2:20][CH2:21]1)=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 76639Benzyl isocyanateHCID 68745687HCID 68745687, compound2×

Product 1

HCID 25171446HCID 25171446, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (30 mg, 0.075 mmol, INTERMEDIATE 15) in dichloromethane (1 ml) was added benzyl isocyanate (10 μl 0.081 mmol). The mixture was stirred for 2 h at room temperature, at which point LC/MS analysis showed a new peak at the desired molecular weight. The reaction mixture was 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. The resulting mixture was repurified by reverse-phase HPLC: 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 (7.9 mg, 0.015 mmol, 19.79% yield). Mass spectrum (ESI) 536.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=7.0 Hz, 2H), 7.94 (d, J=7.0 Hz, 2H), 7.93 (d, J=1.5 Hz, 1H), 7.52 (s, 1H), 7.27-7.35 (m, 4H), 6.55 (br s, 1H), 4.43 (s, 2H), 3.99 (br d, J=11.0 Hz, 2H), 3.47 (septet, J=5.5 Hz, 1H), 3.42 (t, J=5.5 Hz, 2H), 2.86 (br t, J=10.5 Hz, 2H), 2.73 (s, 3H), 1.90 (m, 1H), 1.81 (br d, J=10.0 Hz, 2H), 1.46 (d, J=5.5 Hz, 6H), 1.31 (m, 2H).

Workup

  1. customThe reaction mixture was purified by flash chromatography on a Biotage Horizon, 25S column
  2. washeluting with 1 column volume of 100% dichloromethane
  3. customThe resulting mixture was repurified by reverse-phase HPLC
  4. washKromasil 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
  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-b8e82b592c5a4dc7abf3a11662d40b09
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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