1-Chloroethyl chloroformate → (R)-5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-N-(morpholin-2-ylmethyl)-1-phenyl-1H-pyrazole-3-carboxamide

HRID 522088Notes

Reaction equation

HRID 522088 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:22]([C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][N:26]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18](O)=[O:19])[CH:8]=1)=[O:5].C([N:39]1[CH2:44][CH2:43][O:42][C@@H:41]([CH2:45][NH2:46])[CH2:40]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:24]=[CH:23][C:22]([C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][N:26]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]([NH:46][CH2:45][C@@H:41]2[O:42][CH2:43][CH2:44][NH:39][CH2:40]2)=[O:19])[CH:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 5213051-Chloroethyl chloroformateHCID 6932054(S)-(4-benzylmorpholin-2-yl)methanamineHCID 1184971095-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 118497187(R)-5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-N-(morpholin-2-ylmethyl)-1-phenyl-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared according to the method described for Example 3 using 5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 105) and (S)-(4-benzylmorpholin-2-yl)methanamine. The residue was dissolved in DCM and treated with 1-chloroethyl chloroformate (37.2 μL, 0.192 mmol) and stirred at room temperature for 4 hours. The reaction was concentrated in vacuo, methanol (4 mL) was added, and the resulting solution stirred for 2 hours at 65° C. The reaction was concentrated in vacuo, and the residue purified by elution through an SCX cartridge followed by silica gel column chromatography eluting with 2% NH3(aq) and 8% propan-2-ol in dichloromethane.

Workup

  1. concentrationThe reaction was concentrated in vacuo, methanol (4 mL)
  2. additionwas added
  3. stirringthe resulting solution stirred for 2 hours at 65° C
  4. concentrationThe reaction was concentrated in vacuo
  5. customthe residue purified by elution through an SCX cartridge
  6. washeluting with 2% NH3(aq) and 8% propan-2-ol in dichloromethane

Sources & evidence

ORD record
ord-fbb3c0122e0f49eda6839d086221db32
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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