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

HRID 630665Notes

Reaction equation

HRID 630665 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].[NH2:41][CH2:42][C:43]([NH:45][C@H:46]([C:68]([NH2:70])=[O:69])[CH2:47][S:48][C:49]([C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:44].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]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:7][C:8]1[CH:9]=[CH:10][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]([NH:41][CH2:42][C:43]([NH:45][C@H:46]([C:68]([NH2:70])=[O:69])[CH2:47][S:48][C:49]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[O:44])=[O:20])=[O:14])=[CH:30][CH:31]=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 89544878(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acidHCID 89554940Glycyl-S-trityl-L-cysteinamide

Product 1

HCID 89545100N-{(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)-carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]butanoyl}glycyl-S-trityl-L-cysteinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

559 mg (0.99 mmol) of the compound from example 2A was dissolved in 15 ml dichloromethane. 415 mg (0.99 mmol) of the compound from example 18A, 173 μl (0.99 mmol) N,N-diisopropylethylamine and 376 mg (0.99 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 dissolved in dichloromethane and chromatographed over approx. 70 ml silica gel. Solvents used were dichloromethane, dichloromethane/methanol 20/1 to dichloromethane/methanol 5/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 860 mg (0.69 mmol, 70% of theory) of the desired product.

Workup

  1. customFrom the reaction mixture the solvent was removed under reduced pressure
  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-36e120c09ecb4e46a551c93c7c8a620d
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

Loading…