Diisopropylethylamine → N-[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-3-[(tert-butoxycarbonyl)amino]-L-alanyl-S-trityl-L-cysteinamide

HRID 630670Notes

Reaction equation

HRID 630670 reaction equation
[CH2:1]([O:4][C:5](=[O:39])[C@@H:6]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:7][C:8]1[CH:30]=[CH:29][C:11]([O:12][C:13]([NH:15][C@H:16]([C:26](O)=[O:27])[CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:14])=[CH:10][CH:9]=1)[CH:2]=[CH2:3].[C:40]([S:59][CH2:60][C@@H:61]([C:63]([NH2:65])=[O:64])[NH2:62])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=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:39])[C@@H:6]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]([NH:15][C@H:16]([C:26]([NH:62][C@H:61]([C:63]([NH2:65])=[O:64])[CH2:60][S:59][C:40]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)=[O:27])[CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:14])=[CH:29][CH:30]=1)[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 89544774N-[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-3-[(tert-butoxycarbonyl)amino]-L-alanine

Product 1

HCID 89545055N-[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-3-[(tert-butoxycarbonyl)amino]-L-alanyl-S-trityl-L-cysteinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1.23 g (2.23 mmol) of the compound from example 24A was dissolved in 25 ml dichloromethane. 0.81 g (2.23 mmol) S-Trityl-L-cysteinamide, 0.39 ml (2.23 mmol) N,N-diisopropylethylamine and 0.85 g (2.23 mmol) HATU were added. The reaction mixture was stirred at room temperature for 3 h. From the reaction mixture the solvent was removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.). The raw product was dissolved in dichloromethane and chromatographed over approx. 70 ml silica gel. Solvents used were dicloromethane/methanol 20/1 to dichloromethane/methanol 5/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 2.38 g (2.03 mmol, 91% of theory, 76% purity) of the desired product.

Workup

  1. customFrom the reaction mixture the solvent was removed by rotary evaporation (approx. 40° C., approx. 200 mbar, approx. 30 min.)
  2. dissolutionThe raw product was dissolved in dichloromethane
  3. customchromatographed over approx. 70 ml silica gel
  4. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-2cdeea3d923a426da5384cea1300fc42
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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