Pyridine → HCID 178452465, compound

HRID 710265Notes

Reaction equation

HRID 710265 reaction equation
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C@@H:13]3[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]3)=[CH:9][CH:8]=2)[CH:3]=1.N1C=CC=CC=1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1>O1CCCC1.ClCCl.CN(C)C1C=CN=CC=1>[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([NH:1][C:2]2[NH:6][N:5]=[C:4]([C:7]3[CH:8]=[CH:9][C:10]([C@@H:13]4[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]4)=[CH:11][CH:12]=3)[CH:3]=2)=[O:38])=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 678794-Fluorobenzoyl chlorideHCID 178452466HCID 178452466, compound

Product 1

HCID 178452465HCID 178452465, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-Butyl 2-(4-(5-amino-1H-pyrazol-3-yl)phenyl)morpholine-4-carboxylate (100 mg, 0.29 mmol) was dissolved in a mixture of tetrahydrofurane/dichloromethane 2:3 (1.5 ml) then pyridine (46 mg, 0.047 ml, 0.58 mmol) and 4-dimethylaminopyridine (1.7 mg, 0.014 mmol) were added at 0° C. After 5 min, 4-fluorobenzoyl chloride (55.2 mg, 0.348 mmol) was addded and the reaction mixture was stirred at 0° C. for 1 h. The cooling bath was removed and the reaction mixture was allowed to stir at room temperature overnight. The reaction was quenched by addition of 1M citric acid (3 ml) and was extracted with ethyl acetate (5 ml). The organic layer was dried over MgSO4 and evaporated. The crude material was purified by flash chromatography (silica gel, hepatne/ethyl acetate 1:1). Isolation of an off-white solid (100 mg, 74%), MS (ISP): 411.2 (100%, [M-tBu+H]+), 467.2 (66%, [M+H]+).

Workup

  1. customThe cooling bath was removed
  2. stirringto stir at room temperature overnight
  3. customThe reaction was quenched by addition of 1M citric acid (3 ml)
  4. extractionwas extracted with ethyl acetate (5 ml)
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated
  7. customThe crude material was purified by flash chromatography (silica gel, hepatne/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-a2e214322d7843a79705e65c0401916f
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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