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

HRID 630662Notes

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][C@@H:62]([C:64]([NH:66][CH2:67][C:68]([NH2:70])=[O:69])=[O:65])[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]([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:63][C@H:62]([C:64]([NH:66][CH2:67][C:68]([NH2:70])=[O:69])=[O:65])[CH2:61][S:60][C:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([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)=[O:20])=[O:14])=[CH:30][CH:31]=1)[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 60 °C

Procedure

173 mg (0.31 mmol) of the compound from example 2A was dissolved in 10 ml dichloromethane. 128 mg (0.31 mmol) S-Trityl-L-cysteinylglycinamide, 53 μl (0.31 mmol) N,N-diisopropylethyl-amine and 116 mg (0.31 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 57 mg (0.02 mmol, 18% of theory) of the desired product.

Workup

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

Sources & evidence

ORD record: ord-2ab04acc1ebe4499832ac7a53b8bd35a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315543B2

Reaction notes

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