Triethylamine → HCID 86673873, compound

HRID 1527559Notes

Reaction equation

HRID 1527559 reaction equation
[Cl:1][C:2]1[C:3]([F:37])=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:14][C@@H:13]2[C@@H:11]([CH2:12]2)[N:10]1[C:15](=[O:33])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH2:27][CH2:28][OH:29])[CH:24]=2)[N:19]([C:30]([NH2:32])=[O:31])[CH:18]=1)=[O:8].CCN(CC)CC.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>C(Cl)Cl>[C:30]([N:19]1[C:20]2[C:25](=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][S:46]([CH3:45])(=[O:48])=[O:47])=[CH:22][CH:21]=2)[C:17]([CH2:16][C:15]([N:10]2[C@H:9]([C:7](=[O:8])[NH:6][CH2:5][C:4]3[CH:34]=[CH:35][CH:36]=[C:2]([Cl:1])[C:3]=3[F:37])[CH2:14][C@@H:13]3[C@H:11]2[CH2:12]3)=[O:33])=[CH:18]1)(=[O:31])[NH2:32]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 68283774HCID 68283774, compound

Product 1

HCID 86673873HCID 86673873, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 453: 3-{2-[(1R,3S,5R)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-5-(2-hydroxy-ethoxy)-indole-1-carboxylic acid amide (45 mg, 0.08 mmol) and Et3N (56 μL, 0.41 mmol) in CH2Cl2 (1 mL) at 0° C. was added methanesulfonyl chloride (31 μL, 0.41 mmol) and the white suspension was stirred at RT under nitrogen overnight. Et3N (56 μL, 0.41 mmol) and methanesulfonyl chloride (31 μL, 0.41 mmol) were added and the mixture was further stirred for 1.5 h to complete the reaction. The reaction mixture was quenched by addition of saturated aqueous NaHCO3, extracted with CH2Cl2, dried (Na2SO4) and evaporated in vacuo. The crude residue was purified by column chromatography on silica gel (eluent: EtOAc to EtOAc/acetone 1-1). TLC, Rf (EtOAc)=0.2; MS (UPLC/MS): 607.4/609.3 [M+H]+, 629.2/631.2 [M+Na]+, 562.2/564.1 [M−CONH2]−, 651.3/653.3 [M+HCOO]−; tR (HPLC conditions f): 1.88 min.

Workup

  1. stirringthe mixture was further stirred for 1.5 h
  2. customthe reaction
  3. customThe reaction mixture was quenched by addition of saturated aqueous NaHCO3
  4. extractionextracted with CH2Cl2
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe crude residue was purified by column chromatography on silica gel (eluent: EtOAc to EtOAc/acetone 1-1)
  8. custom1.88 min.

Sources & evidence

ORD record
ord-63cd64fdc36e4d4882eb7fa4f414f658
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…