Potassium Carbonate → ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

HRID 1503222Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].Cl.C1(N(CCC(OCC)=O)C(C2C=CC3N(C)C(CNC4C=CC(C(=N)N)=CC=4)=NC=3C=2)=O)C=CC=CC=1.Cl.[C:46]([C:49]1[CH:54]=[CH:53][C:52]([NH:55][CH2:56][C:57]2[N:61]([CH3:62])[C:60]3[CH:63]=[CH:64][C:65]([C:67]([N:69]([CH2:76][CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79])[C:70]4[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=4)=[O:68])=[CH:66][C:59]=3[N:58]=2)=[CH:51][CH:50]=1)(=[NH:48])[NH2:47].[Cl:83][C:84]([O:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH3:92])=[O:85]>CC(C)=O.O>[CH3:92][CH2:91][CH2:90][CH2:89][CH2:88][CH2:87][O:86][C:84](/[N:48]=[C:46](\[NH2:47])/[C:49]1[CH:50]=[CH:51][C:52]([NH:55][CH2:56][C:57]2[N:61]([CH3:62])[C:60]3[CH:63]=[CH:64][C:65]([C:67]([N:69]([C:70]4[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=4)[CH2:76][CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79])=[O:68])=[CH:66][C:59]=3[N:58]=2)=[CH:53][CH:54]=1)=[O:85].[ClH:83].[C:46]([C:49]1[CH:54]=[CH:53][C:52]([NH:55][CH2:56][C:57]2[N:61]([CH3:62])[C:60]3[CH:63]=[CH:64][C:65]([C:67]([N:69]([CH2:76][CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79])[C:70]4[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=4)=[O:68])=[CH:66][C:59]=3[N:58]=2)=[CH:51][CH:50]=1)(=[NH:47])[NH2:48]

Participants

Conditions

Temperature: 10 °C

Procedure

350 mL acetone, 250 mL water and 32.2 g potassium carbonate were stirred in round bottom flask at 25° C. The reaction mixture was cooled to 10° C. and 100 g of 1-methyl-2-[N-(4-amidinophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxy carbonylethyl)amide hydrochloride of Formula (E) was added. 15 mL acetone and 16.8 mL n-hexyl chloroformate were added to the reaction mixture and stirred for 1 hour. The precipitated product was filtered and washed with mixture of acetone and water. The wet-cake was dissolved in acetone and stirred for 30 min. The product was obtained by addition of water followed by filtration. The wet-cake thus obtained was washed with acetone and dried to obtain dabigatran etexilate of Formula (E). 50 g dabigatran etexilate and 500 mL ethyl acetate were stirred at 25° C. The reaction mixture was charcoalized and filtered. The filtrate was heated 75° C. to 80° C. and stirred for 30 minutes and cooled to 25° C. to 35° C. The reaction mixture was filtered and washed with ethyl acetate to obtain pure dabigatran etexilate of Formula (F).

Workup

filtrationThe precipitated product was filtered
washwashed with mixture of acetone and water
dissolutionThe wet-cake was dissolved in acetone
stirringstirred for 30 min
customThe product was obtained by addition of water
filtrationfollowed by filtration
customThe wet-cake thus obtained
washwas washed with acetone
customdried

Sources & evidence

ORD record: ord-b499dbace31e43b8a2ac2f33a8ddf0e8
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212166B2

Reaction notes

Loading…