Diisopropylethylamine → Allyl O-[(4-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-3-[(tert-butoxycarbonyl)-(methyl)amino]-4-oxobutyl)carbamoyl]-N-(tert-butoxycarbonyl)-L-tyrosinate

HRID 630654Notes

Reaction equation

HRID 630654 reaction equation
[CH2:1]([O:4][C:5](=[O:41])[C@@H:6]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:7][C:8]1[CH:32]=[CH:31][C:11]([O:12][C:13]([NH:15][CH2:16][CH2:17][CH:18]([N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH3:23])[C:19]([OH:21])=O)=[O:14])=[CH:10][CH:9]=1)[CH:2]=[CH2:3].[C:42]([S:61][CH2:62][C@@H:63]([C:65]([NH2:67])=[O:66])[NH2:64])([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=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:41])[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][CH:18]([N:22]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH3:23])[C:19]([NH:64][C@@H:63]([CH2:62][S:61][C:42]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:65]([NH2:67])=[O:66])=[O:21])=[CH:31][CH:32]=1)[NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44432703(2R)-2-amino-3-((triphenylmethyl)sulfanyl)propanamideHCID 895455684-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)(methyl)amino]butanoic acid

Product 1

HCID 89544630Allyl O-[(4-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-3-[(tert-butoxycarbonyl)-(methyl)amino]-4-oxobutyl)carbamoyl]-N-(tert-butoxycarbonyl)-L-tyrosinate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

2.24 g (3.86 mmol) of the compound from example 7A was dissolved in 100 ml dichloromethane. 1.401 g (3.86 mmol) S-Trityl-L-cysteinamide, 0.67 ml (3.86 mmol) N,N-diisopropylethylamine and 1.47 g (3.86 mmol) HATU were added. The reaction mixture was split into 5 portions. The portions were heated for 30 min in a sealed tube at 60° C. in a microwave synthesizer. From the combined reaction mixture the solvent was removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.). 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 3.26 g (2.75 mmol, 71% of theory, 78% purity) of the desired product as a mixture of diastereomers.

Workup

  1. customThe reaction mixture was split into 5 portions
  2. customFrom the combined reaction mixture the solvent
  3. customwas removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.)
  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 3.26 g (2.75 mmol, 71% of theory, 78% purity) of the desired product as a mixture of diastereomers

Sources & evidence

ORD record
ord-3189ae355c1541098230960ddad6ced2
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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