Chloroform → (7R)-7-({({(2R)-1-({(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-2-pyrrolidinyl}carbonyl)-2-pyrrolidinyl}carbonyl)amino}methyl)-5-azoniaspiro[4.5]decane chloride

HRID 394044Notes

Reaction equation

HRID 394044 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7](=[O:28])[CH2:8][C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@H:4]([C:29]([N:31]2[CH2:35][CH2:34][CH2:33][C@@H:32]2[C:36]([NH:38][CH2:39][C@H:40]2[CH2:45][CH2:44][CH2:43][NH:42][CH2:41]2)=[O:37])=[O:30])[CH2:3]1.C(NCC)C.Br[CH2:52][CH2:53][CH2:54][CH2:55]Br.C(Cl)(Cl)[Cl:58]>>[Cl-:58].[OH:1][C@H:2]1[CH2:6][N:5]([C:7](=[O:28])[CH2:8][C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:4]([C:29]([N:31]2[CH2:35][CH2:34][CH2:33][C@@H:32]2[C:36]([NH:38][CH2:39][C@H:40]2[CH2:45][CH2:44][CH2:43][N+:42]3([CH2:55][CH2:54][CH2:53][CH2:52]3)[CH2:41]2)=[O:37])=[O:30])[CH2:3]1

Participants

5

Reactant 4

HCID 6212Chloroform2×HCID 8021DiethylamineHCID 80561,4-DibromobutaneHCID 12149960(2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide

Product 1

HCID 69910148(7R)-7-({({(2R)-1-({(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-2-pyrrolidinyl}carbonyl)-2-pyrrolidinyl}carbonyl)amino}methyl)-5-azoniaspiro[4.5]decane chloride

Procedure

The method of Japan Kokai (laid-open) No. Sho 62(1987)-215588 A1 was followed. In 0.6 ml of chloroform, 41 mg of (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide, 0.014 ml of diethylamine and 0.032 ml of 1,4-dibromobutane were dissolved, and the solution was allowed to stand in a hermetically sealed vessel for 6 days. The reaction liquid was diluted with chloroform and the solvent was distilled off under reduced pressure. The resultant residue was dissolved in a mixture of ultrapure water 0.6 ml/methanol 0.1 ml, and developed on a reversed phase medium pressure liquid chromatography [ODS-AQ 120-S50 (YMC). The product was purified and anion-exchanged by pouring 20 ml of saturated brine, washing with 150 ml of ultrapure water, and eluting from methanol/water=1/1, to provide 45 mg of the title compound as a white solid.

Workup

  1. customThe reaction liquid
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionThe resultant residue was dissolved in a mixture of ultrapure water 0.6 ml/methanol 0.1 ml
  4. customThe product was purified
  5. additionanion-exchanged by pouring 20 ml of saturated brine
  6. washwashing with 150 ml of ultrapure water
  7. washeluting from methanol/water=1/1

Sources & evidence

ORD record
ord-bab2be652f6c420597fbb00c94f080e9
Source dataset
uspto-grants-2004_10
Patent number
US06809108B1

Reaction notes

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