Acetic Acid → HCID 69288008, compound

HRID 2375793Notes

Reaction equation

HRID 2375793 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][CH2:5][C:6]1[C:10]([CH3:11])=[C:9]([C:12](=[O:23])[NH:13][CH:14]2[CH2:19][CH2:18][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]2)[NH:8][C:7]=1[CH3:24].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:33][C:34]1[CH:38]=[C:37]([C:39]2[S:40][C:41]([Cl:44])=[CH:42][CH:43]=2)[O:36][N:35]=1.C(O)(=O)C>CN(C=O)C>[CH3:1][O:2][C:3](=[O:25])[CH2:4][CH2:5][C:6]1[C:10]([CH3:11])=[C:9]([C:12](=[O:23])[NH:13][CH:14]2[CH2:15][CH2:16][N:17]([CH:20]([CH3:21])[CH3:22])[CH2:18][CH2:19]2)[N:8]([CH2:33][C:34]2[CH:38]=[C:37]([C:39]3[S:40][C:41]([Cl:44])=[CH:42][CH:43]=3)[O:36][N:35]=2)[C:7]=1[CH3:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 10796Cesium carbonate2×HCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 69289368HCID 69289368, compound

Product 1

HCID 69288008HCID 69288008, compoundYield 38.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

55 mg (0.16 mmol) of 3-[5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2,4-dimethyl-1H-pyrrol-3-yl]-propionic acid methyl ester were dissolved in DMF (5 mL). Subsequently 103 mg (2 equiv.) of Cs2CO3 and 65.8 mg (1.5 equiv.) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added and the resulting mixture was stirred for 4 h at 800 C. Because of low conversion 206 mg (4 equiv.) of Cs2CO3 were added stirring was continued for 7 h at 80° C. The reaction mixture was acidified by the addition of acetic acid and concentrated. The residue was purified by preparative HPLC(CH3CN/H2O gradient+0.05% formic acid) to give 3-[1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2,4-dimethyl-1H-pyrrol-3-yl]-propionic acid methyl ester (34 mg) as a colorless amorphous material. MS (ESI+): m/e=548 [M+H]+, chloro pattern.

Workup

  1. stirringstirring
  2. waitwas continued for 7 h at 80° C
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC(CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-30e2951b961144e0a7ac7d6016fac644
Source dataset
uspto-grants-2008_12
Patent number
US07465806B2

Reaction notes

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