Thiophene → cis-4-amino-5-chloro-N-[1-(3,3-dimethyl-1,5-dioxaspiro[5.5]undec-9-yl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide

HRID 2248636Notes

Reaction equation

HRID 2248636 reaction equation
[CH3:1][C:2]1([CH3:14])[CH2:7][O:6][C:5]2([CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[O:4][CH2:3]1.[NH2:15][C:16]1[C:32]([Cl:33])=[CH:31][C:19]([C:20]([NH:22][C@H:23]2[CH2:28][CH2:27][NH:26][CH2:25][C@H:24]2[O:29][CH3:30])=[O:21])=[C:18]([O:34][CH3:35])[CH:17]=1.S1C=CC=C1.[H][H]>CO.[Pt]>[NH2:15][C:16]1[C:32]([Cl:33])=[CH:31][C:19]([C:20]([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([CH:10]3[CH2:11][CH2:12][C:5]4([O:6][CH2:7][C:2]([CH3:14])([CH3:1])[CH2:3][O:4]4)[CH2:8][CH2:9]3)[CH2:25][C@H:24]2[O:29][CH3:30])=[O:21])=[C:18]([O:34][CH3:35])[CH:17]=1

Participants

7

Reactant 4

HCID 8030ThiopheneHCID 5879683,3-Dimethyl-1,5-dioxaspiro(5.5)undecan-9-oneHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamideHCID 178418361HCID 178418361, compound

Product 1

HCID 67922714cis-4-amino-5-chloro-N-[1-(3,3-dimethyl-1,5-dioxaspiro[5.5]undec-9-yl)-3-methoxy-4-piperidinyl]-2-methoxybenzamideYield 62.6%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of 10 parts of 3,3-dimethyl-1,5-dioxaspiro[5.5]undecan-9-one, 9.42 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide, 1 part of a solution of thiophene in methanol 4% and 200 parts of methanol was hydrogenated at normal pressure and at room temperature with 2 parts of platinum-on-charcoal catalyst 5%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filterate was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried in vacuo at 60° C., yielding 9.33 parts (62.6%) of cis-4-amino-5-chloro-N-[1-(3,3-dimethyl-1,5-dioxaspiro[5.5]undec-9-yl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 187.5° C. (compound 92).

Workup

  1. filtrationthe catalyst was filtered off
  2. customthe filterate was evaporated
  3. customThe residue was crystallized from acetonitrile
  4. filtrationThe product was filtered off
  5. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-ed2848c597a9458780bf76f98bcb1de6
Source dataset
uspto-grants-1991_08
Patent number
US05041454

Reaction notes

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