Morpholine → 2-(2-morpholinopyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide

HRID 85102Notes

Reaction equation

HRID 85102 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([NH:19][C:20]4[S:21][CH:22]=[CH:23][N:24]=4)=[O:18])[C:10]=3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>CS(C)=O.O>[Cl:1][C:2]1[C:7]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([NH:19][C:20]4[S:21][CH:22]=[CH:23][N:24]=4)=[O:18])[C:10]=3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[O:28]1[CH2:29][CH2:30][N:25]([C:2]2[C:7]([C:8]3[NH:12][C:11]4[CH:13]=[CH:14][CH:15]=[C:16]([C:17]([NH:19][C:20]5[S:21][CH:22]=[CH:23][N:24]=5)=[O:18])[C:10]=4[N:9]=3)=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 2

HCID 8083MorpholineHCID 866537882-(2-Chloropyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide

Product 2

HCID 446006392-(2-morpholinopyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamideYield 120.7%HCID 866537882-(2-Chloropyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

2-(2-Chloropyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide 9 was prepared according to the general procedure outlined above using the appropriate aldehyde component. A mixture containing this material, namely 2-(2-chloropyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide (9; 19 mg, 0.053 mmol) and morpholine (48; 46 mg, 0.53 mmol) in DMSO (1.2 mL) were stirred at 140° C. in a microwave reactor for 25 min. The reaction mixture was cooled to room temperature and diluted with water. The precipitated solids were collected by filtration and dried. The solids were redissolved in EtOAc and enough petroleum ether was added to precipitate the product out again. The solids were collected by filtration, washed with MeOH and dried to afford 2-(2-morpholinopyridin-3-yl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 250) as a white solid (13 mg, 60%). MS (ESI) calcd for C20H18N6O2S (m/z): 406.12; found: 407 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe precipitated solids were collected by filtration
  3. customdried
  4. dissolutionThe solids were redissolved in EtOAc
  5. additionenough petroleum ether was added
  6. customto precipitate the product out again
  7. filtrationThe solids were collected by filtration
  8. washwashed with MeOH
  9. customdried

Sources & evidence

ORD record
ord-4377b2a8f7b341b4be9cfa3c6fbf1cff
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

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