4-Amino-2-[(tert-butoxycarbonyl)(methyl)amino]butanoic acid → 4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)(methyl)amino]butanoic acid

HRID 630653Notes

Reaction equation

HRID 630653 reaction equation
[CH2:1]([O:4][C:5](=[O:35])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](OC2C=CC([N+]([O-])=O)=CC=2)=[O:24])=[CH:18][CH:17]=1)[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:2]=[CH2:3].[NH2:36][CH2:37][CH2:38][CH:39]([N:43]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH3:44])[C:40]([OH:42])=[O:41]>ClCCl>[CH2:1]([O:4][C:5](=[O:35])[C@@H:6]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([NH:36][CH2:37][CH2:38][CH:39]([N:43]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH3:44])[C:40]([OH:42])=[O:41])=[O:24])=[CH:18][CH:17]=1)[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 895448434-Amino-2-[(tert-butoxycarbonyl)(methyl)amino]butanoic acidHCID 117612078Allyl-N-(tert-butoxycarbonyl)-O-[(4-nitrophenoxy)carbonyl]-L-tyrosinate

Product 1

HCID 895455684-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)(methyl)amino]butanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

0.931 g (1.92 mmol) of the compound from example 1A was dissolved in 30 ml dichloromethane. 0.455 g (1.92 mmol) of the compound from example 6A was added. The reaction mixture was split into 2 portions. The portions were heated for 30 min in a sealed tube at 80° C. in a microwave synthesizer. From the combined reaction mixture the solvent was removed under reduced pressure. The raw product was purified by preparative RP-HPLC on a C18 column with a water methanol gradient from 9/1 to 1/9. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 0.523 g (0.85 mmol, 44% of theory) of the desired product as a mixture of 2 diastereomers.

Workup

  1. customThe reaction mixture was split into 2 portions
  2. customFrom the combined reaction mixture the solvent
  3. customwas removed under reduced pressure
  4. customThe raw product was purified by preparative RP-HPLC on a C18 column with a water methanol gradient from 9/1 to 1/9
  5. concentrationconcentrated to dryness under reduced pressure
  6. additionThis gave 0.523 g (0.85 mmol, 44% of theory) of the desired product as a mixture of 2 diastereomers

Sources & evidence

ORD record
ord-7a1696a531f54f83abe01f2aa7fea407
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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