4-Methylmorpholine → tert-butyl (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acid

HRID 2304249Notes

Reaction equation

HRID 2304249 reaction equation
Cl.[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([OH:15])=O)=[CH:10][CH:11]=2)[CH:6]=[CH:5][N:4]=1.OC1C2N=NNC=2C=CC=1.CN1CCOCC1.Cl.[C:34]([C@H:38]([O:42][CH:43]1[CH2:48][CH2:47][N:46]([C:49](=[O:53])[CH:50]([NH2:52])[CH3:51])[CH2:45][CH2:44]1)[C:39]([OH:41])=[O:40])([CH3:37])([CH3:36])[CH3:35].CN(C)CCCN=C=NCC>CN(C)C=O>[C:34]([C@H:38]([O:42][CH:43]1[CH2:48][CH2:47][N:46]([C:49](=[O:53])[CH:50]([NH:52][C:13]([C:9]2[CH:8]=[C:7]3[C:12](=[CH:11][CH:10]=2)[C:3]([NH2:2])=[N:4][CH:5]=[CH:6]3)=[O:15])[CH3:51])[CH2:45][CH2:44]1)[C:39]([OH:41])=[O:40])([CH3:36])([CH3:35])[CH3:37]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 697812331-Aminoisoquinoline-6-carboxylic acid hydrochlorideHCID 86588685tert-butyl (S)-[[1-(2-amino-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 86588687tert-butyl (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4-yl]oxy]acetic acidYield 92.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.33 g (1-amino-6-isoquinolinyl)carboxylic acid hydrochloride in 20 mL of N,N-dimethylformamide were added 0.34 g hydroxybenztriazole, 0.504 mL N-methylmorpholine, 0.525 g tert-butyl (S)-[[1-(2-amino-1-oxopropyl)piperidin-4-yl]oxy]acetic acid hydrochloride and 0.425 g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. After stirring at room temperature for three days the mixture was concentrated. Dichloromethane and 1% aqueous sodium hydrogencarbonate were added to the residue and the organic layer was separated. The aqueous layer was washed four times with dichloromethane, the combined organic layers dried (sodium sulfate) and concentrated. The residue was purified by chromatography (silica gel, dichloromethane/methanol: 10/1 v/v followed by a purification using silica gel, ethyl acetate/methanol: 10/1 v/v) to give 0.619 g of the title compound.

Workup

  1. concentrationwas concentrated
  2. additionDichloromethane and 1% aqueous sodium hydrogencarbonate were added to the residue
  3. customthe organic layer was separated
  4. washThe aqueous layer was washed four times with dichloromethane
  5. dry with materialthe combined organic layers dried (sodium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (silica gel, dichloromethane/methanol
  8. custom10/1 v/v followed by a purification

Sources & evidence

ORD record
ord-5d7e22510f6541209f753e9a58f58abc
Source dataset
uspto-grants-2002_08
Patent number
US06432955B1

Reaction notes

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