Pivaloyl chloride → HCID 178472060, compound

HRID 1527139Notes

Reaction equation

HRID 1527139 reaction equation
CCCCCC[O:7][C:8](/[N:10]=[C:11](\[NH2:46])/[C:12]1[CH:13]=[CH:14][C:15]([NH:18][CH2:19][C:20]2[N:28]([CH3:29])[C:27]3[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=4)[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:16][CH:17]=1)=[O:9].NC1C=C(C=CC=1NC)C(N(C1C=CC=CN=1)CCC(OCC)=O)=O.O1C(=O)N=C(C2C=CC(NCC(O)=O)=CC=2)N1.C(Cl)(=O)C(C)(C)C>>[O:7]1[C:8](=[O:9])[N:10]=[C:11]([C:12]2[CH:13]=[CH:14][C:15]([NH:18][CH2:19][C:20]3[N:28]([CH3:29])[C:27]4[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]5[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=5)[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:23][C:22]=4[N:21]=3)=[CH:16][CH:17]=2)[NH:46]1

Participants

5

Reactant 4

HCID 62493Pivaloyl chlorideHCID 6445226ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoateHCID 11982993N-(3-Amino-4-(methylamino)benzoyl)-N-2-pyridinyl-beta-alanine ethyl ester2×HCID 1785258632-[4-(5-oxo-2H-1,2,4-oxadiazol-3-yl)anilino]acetic acid2×

Product 1

HCID 178472060HCID 178472060, compound

Procedure

U.S. Pat. No. 7,202,368 describes an alternative process for the synthesis of dabigatran etexilate (see Scheme 2). Example 3 describes the condensation between ethyl 3-{[3-amino-4-(methylamino)benzoyl](pyridin-2-yl)amino}propanoate (compound II) and 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid (compound VII) in the presence of a coupling agent such as N,N′-carbonyldiimidazole (CDI), propanephosphonic anhydride (PPA), or pivaloyl chloride, to give ethyl 3-{[(2-{[(4-{1,2,4-oxadiazol-5-on-3-yl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate (compound VIII), which is subsequently hydrogenated (Example 4) in the presence of a palladium catalyst to give ethyl 3-{[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate (compound V). Then, Example 5 describes the acylation of compound V with n-hexyl chloroformate (compound VI) to give dabigatran etexilate. Finally, Example 6 describes the conversion of dabigatran etexilate into its mesylate salt. Although the patent describes the HPLC purities of intermediate compounds II, VII, VIII and V, no information is given neither about the purity of the isolated dabigatran etexilate nor about its mesylate salt.

Sources & evidence

ORD record
ord-5859b5546d844541a069474e951b578f
Source dataset
uspto-grants-2015_07
Patent number
US09086390B2

Reaction notes

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