N-methyl-2-pyrrolidone → Rivaroxaban

HRID 425237Notes

Reaction equation

HRID 425237 reaction equation
[OH:1][C@H:2]([CH2:13][NH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][C:22]2=[O:27])=[CH:17][CH:16]=1)[CH2:3][NH:4][C:5]([C:7]1[S:8][C:9]([Cl:12])=[CH:10][CH:11]=1)=[O:6].CN1CCC[C:30]1=[O:34].C1N=CN(C(N2C=NC=C2)=O)C=1>C1(C)C=CC=CC=1>[Cl:12][C:9]1[S:8][C:7]([C:5]([NH:4][CH2:3][C@@H:2]2[O:1][C:30](=[O:34])[N:14]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][C:22]4=[O:27])=[CH:19][CH:20]=3)[CH2:13]2)=[O:6])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 682631,1'-CarbonyldiimidazoleHCID 100015745-Chloro-N-((2R)-2-hydroxy-3-((4-(3-oxo-4-morpholinyl)phenyl)amino)propyl)-2-thiophenecarboxamide

Product 1

HCID 9875401Rivaroxaban

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
81.5 °C

Procedure

25 g of N-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}-5-chlorothiophene-2-carboxamide (X) are suspended at from 20 to 25° C. in 250 ml of toluene and admixed with 37.5 ml of 1-methyl-2-pyrrolidone and 11.9 g of N,N-carbonyldiimidazole. The reaction mixture is heated to from 80 to 83° C. for 20 minutes and subsequently heated to 115° C. for one hour. After cooling to 20° C., the precipitated reaction product is filtered off with suction, washed twice with 25 ml each time of water and dried at 60° C. under reduced pressure.

Workup

  1. temperaturesubsequently heated to 115° C. for one hour
  2. temperatureAfter cooling to 20° C.
  3. customthe precipitated reaction product
  4. filtrationis filtered off with suction
  5. washwashed twice with 25 ml each time of water
  6. customdried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-060b9569b60c48e98ce2d6e4da1f19bf
Source dataset
uspto-grants-2012_01
Patent number
US08106192B2

Reaction notes

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