4-Fluorophenyl isocyanate → HCID 22048658, compound

HRID 1832256Notes

Reaction equation

HRID 1832256 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]=[C:31]=[O:32])=[CH:26][CH:25]=1>C1COCC1.O>[F:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([NH:1][CH2:2][CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:20])[CH3:21])[CH:14]=[CH:15][CH:16]=3)[CH2:7][CH2:6]2)=[O:32])=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 16757470N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}2-methylpropanamide

Product 1

HCID 22048658HCID 22048658, compoundYield 10.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}-2-methylpropanamide (26.4 mg, 0.0870 mol), 1-fluoro-4-isocyanatobenzene (11.9 mg, 0.0870 mmol), in THF (1.00 mL) was stirred for 12 h at 25° C. The resulting crude mixture was diluted with water (10 mL), the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were concentrated in vacuo and the residue was purified by preparative TLC using 2.5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product N-{3-[1-(3-{[(4-fluoroanilino)carbonyl]amino}propyl)-4-piperidinyl]phenyl}-2-methylpropanamide (4.18 mg, 10.9%): 1H NMR (400 MHz, CDCl3) 7.45 (q, 2H, J=4.7 Hz), 7.23–7.21 (m, 4H), 7.05 (t, 4H, J=7.8 Hz), 6.75 (m, 1H), 4.05 (m, 1H), 3.19 (s, 1H), 2.71 (m, 1H), 2.53 (m, 1H), 2.26–2.21 (m, 3H), 1.80–1.60 (m, 9H), 1.25 (d, 6H, J=6.4 Hz); ESMS m/e: 439.4 (M+H)+.

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2 (3×20 mL)
  2. concentrationThe combined organic layers were concentrated in vacuo
  3. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-3ce44495c8824dc4bed3f1d64a40c73d
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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