Ammonia → HCID 58822174, compound

HRID 459563Notes

Reaction equation

HRID 459563 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]1[CH2:18][CH:17]([CH2:19][OH:20])[CH2:16][C@H:15]1[NH:21][C:22]([C:24]1[S:25][C:26]3[CH2:27][N:28]([CH3:33])[CH2:29][CH2:30][C:31]=3[N:32]=1)=[O:23])=[O:12])=[CH:5]2.[N:34]1[CH:39]=CC=CC=1.ClC(OC1C=CC=CC=1)=[O:42].N>O1CCCC1.CO>[C:39]([O:20][CH2:19][CH:17]1[CH2:18][C@@H:14]([NH:13][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)=[O:12])[C@H:15]([NH:21][C:22]([C:24]2[S:25][C:26]3[CH2:27][N:28]([CH3:33])[CH2:29][CH2:30][C:31]=3[N:32]=2)=[O:23])[CH2:16]1)(=[O:42])[NH2:34]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 1049PyridineHCID 15891Phenyl chloroformateHCID 58822066HCID 58822066, compound

Product 1

HCID 58822174HCID 58822174, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(1R*,2R*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-hydroxymethyl-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine (Stereoisomer A) (200 mg) was suspended in tetrahydrofuran (80 ml), and pyridine (100 μl) was added, and phenyl chloroformate (156 μl) was then added to stir the mixture at room temperature for 10 minutes. A saturated methanol solution (10 ml) of ammonia was added to the reaction mixture, and the mixture was left to stand overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and a 1:9 mixed solvent (100 ml) of methanol and dichloromethane and a 1N aqueous solution (50 ml) of sodium hydroxide were added to the residue to conduct liquid separation. The resultant organic layer was then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1). The thus-obtained colorless amorphous solid was suspended in 1N hydrochloric acid (1 ml), and the suspension was concentrated under reduced pressure to obtain the title compound (151 mg) as a pale yellow solid.

Workup

  1. waitthe mixture was left
  2. waitto stand overnight at room temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiona 1:9 mixed solvent (100 ml) of methanol and dichloromethane and a 1N aqueous solution (50 ml) of sodium hydroxide were added to the residue
  5. customliquid separation
  6. dry with materialThe resultant organic layer was then dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=10:1)
  9. concentrationthe suspension was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2db81a435ab144c8bb9007d0289b05f1
Source dataset
uspto-grants-2007_03
Patent number
US07192968B2

Reaction notes

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