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

HRID 630651ノート

反応式

HRID 630651 の反応式
[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]([OH:21])=O)=[O:14])=[CH:10][CH:9]=1)[CH:2]=[CH2:3].[C:41]([S:60][CH2:61][C@@H:62]([C:64]([NH2:66])=[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>[NH2:66][C:64](=[O:65])[C@@H:62]([NH:63][C:19](=[O:21])[C@@H:18]([NH:22][C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:17][CH2:16][NH:15][C:13]([O:12][C:11]1[CH:10]=[CH:9][C:8]([CH2:7][C@@H:6]([C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:40])[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])=[CH:31][CH:30]=1)=[O:14])[CH2:61][S:60][C:41]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

参加物

6

反応物 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 89544878(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acid

生成物 1

HCID 89554969Allyl O-({(3S)-4-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

2.50 g (4.42 mmol) of the compound from example 2A was dissolved in 100 ml dichloromethane. 1.602 g (4.42 mmol) S-Trityl-L-cysteinamide, 0.77 ml (4.42 mmol) N,N-diisopropylethylamine and 1.68 g (4.42 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 dissolved in dichloromethane and chromatographed over approx. 600 ml silica gel. Solvents used were dichloromethane/ethyl acetate 2/1, dichloromethane/ethyl acetate 1/1, dichloromethane/methanol 20/1 and dichloromethane/methanol 10/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 4.12 g (3.30 mmol, 75% of theory, 73% purity) of the desired product.

後処理

  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. dissolutionThe raw product was dissolved in dichloromethane
  5. customchromatographed over approx. 600 ml silica gel
  6. concentrationconcentrated to dryness under reduced pressure

出典と根拠

ORDレコード
ord-3fa00236e3fe4f7cb6f3a1eda5f5799f
出典データセット
uspto-grants-2016_04
特許番号
US09315543B2

反応ノート

読み込み中…