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Pivaloyl chloride → HCID 178472060, Verbindung

HRID 1527139
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1527139
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
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5

Edukt 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×

Produkt 1

HCID 178472060
HCID 178472060, Verbindung

Versuchsvorschrift

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.

Quellen und Nachweise

ORD-Eintrag
ord-5859b5546d844541a069474e951b578f
Quelldatensatz
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09086390B2

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