4-Fluorobenzoyl chloride → HCID 178457800, compound

HRID 518740Notes

Reaction equation

HRID 518740 reaction equation
O.N1(O)C2C=CC=CC=2N=N1.[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1.[NH2:22][C:23]1[N:27]([C@@H:28]2[CH2:33][CH2:32][C@H:31]([C:34]([NH:36][CH:37]([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)[C:26]2[CH:40]=[C:41]([N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)[CH:42]=[CH:43][C:25]=2[N:24]=1>C(Cl)Cl>[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](/[N:22]=[C:23]2\[NH:24][C:25]3[CH:43]=[CH:42][C:41]([N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[CH:40][C:26]=3[N:27]\2[C@H:28]2[CH2:33][CH2:32][C@@H:31]([C:34](=[O:35])[NH:36][CH:37]([CH3:39])[CH3:38])[CH2:30][CH2:29]2)=[O:18])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 678794-Fluorobenzoyl chlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178457825HCID 178457825, compound

Product 1

HCID 178457800HCID 178457800, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of TEA (0.091 mL, 0.654 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (100 mg, 0.654 mmol) in DCM (2 mL) was added 4-fluorobenzoyl chloride (0.064 mL, 0.545 mmol) dropwise, and the reaction was stirred at RT for 30 minutes. After 30 minutes, the suspension was added to a solution of cis-4-(2-amino-6-morpholino-1H-benzo[d]imidazol-1-yl)-N-isopropylcyclohexanecarboxamide (210 mg, 0.545 mmol) in DCM (5 mL). The reaction was stirred at RT. After 3 days, the reaction mixture was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-10% MeOH in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-morpholino-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a grey powder (95 mg, 34.4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (s, 1H), 8.29 (dd, J=6.1, 8.8 Hz, 2H), 7.73 (d, J=7.5 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J=8.7 Hz, 1H), 7.24 (dd, J=8.8 Hz, 8.8 Hz, 2H), 6.87, (d, J=8.8 Hz, 1H), 4.94 (brs, 1H), 3.90-3.99 (m, 1H), 3.78 (t, J=4.7 Hz, 4H), 3.18 (t, J=4.8 Hz, 4H), 2.74-2.84 (m, 2H), 2.55 (brs, 1H), 2.03-2.11 (m, 2H), 1.67-1.78 (m, 2H), 1.54-1.63 (m, 2H), 1.10 (d, J=6.5 Hz, 6H). MS, m/z (C28H34FN5O3): calcd, 507.3. found, 507.9 [M+H].

Workup

  1. waitAfter 30 minutes
  2. stirringThe reaction was stirred at RT
  3. waitAfter 3 days
  4. concentrationthe reaction mixture was concentrated
  5. custompurified by column chromatography
  6. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-a1edbc241081417bb3a20c4e477a6a58
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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