Diisopropylethylamine → Allyl-N-(tert-butoxycarbonyl)-O-{[(3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-{[2-(tritylsulfanyl)ethyl]amino}butyl]carbamoyl}-L-tyrosinate

HRID 630661Notes

Reaction equation

HRID 630661 reaction equation
[CH2:1]([O:4][C:5](=[O:40])[C@@H:6]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:7][C:8]1[CH:31]=[CH:30][C:11]([O:12][C:13]([NH:15][CH2:16][CH2:17][C@H:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:19](O)=[O:20])=[O:14])=[CH:10][CH:9]=1)[CH:2]=[CH2:3].[C:41]([S:60][CH2:61][CH2:62][NH2:63])([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[CH2:1]([O:4][C:5](=[O:40])[C@H:6]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13](=[O:14])[NH:15][CH2:16][CH2:17][C@H:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:19](=[O:20])[NH:63][CH2:62][CH2:61][S:60][C:41]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[CH:30][CH:31]=1)[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 262764S-TritylcysteamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89544878(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acid

Product 1

HCID 117893244Allyl-N-(tert-butoxycarbonyl)-O-{[(3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-{[2-(tritylsulfanyl)ethyl]amino}butyl]carbamoyl}-L-tyrosinate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

351 mg (0.63 mmol) of the compound from example 2A was dissolved in 15 ml dichloromethane. 200 mg (0.63 mmol) 2-(Tritylsulfanyl)ethanamine, 0.11 ml (0.63 mmol) N,N-diisopropylethyl-amine and 238 mg (0.63 mmol) HATU were added. The reaction mixture was heated for 30 min in a sealed tube at 60° C. in a microwave synthesizer. From the 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 98 mg (0.110 mmol, 16% of theory) of the desired product.

Workup

  1. customFrom the reaction mixture the solvent was removed under reduced pressure
  2. customThe raw product was purified by preparative RP-HPLC on a C18 column with a water methanol gradient from 9/1 to 1/9
  3. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-705b9693a0e44389b7ba1083d0d46b0b
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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