Diisopropylethylamine → Allyl-O-({(3S)-4-[(6-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)-amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate

HRID 630667ノート

反応式

HRID 630667 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](O)=[O:20])=[O:14])=[CH:10][CH:9]=1)[CH:2]=[CH2:3].[NH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([NH:49][C@@H:50]([CH2:54][S:55][C:56]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]([NH2:53])=[O:52])=[O:48].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]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13](=[O:14])[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][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([NH:49][C@@H:50]([CH2:54][S:55][C:56]([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)([C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=2)[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[C:51]([NH2:53])=[O:52])=[O:48])=[O:20])=[CH:30][CH:31]=1)[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:2]=[CH2:3]

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 89544878(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-amino}-2-[(tert-butoxycarbonyl)amino]butanoic acidHCID 895450906-Amino-N-[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]hexanamide

生成物 1

HCID 89554992Allyl-O-({(3S)-4-[(6-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)-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

457 mg (0.81 mmol) of the compound from example 2A was dissolved in 15 ml dichloromethane. 384 mg (0.81 mmol) of the compound from example 21A, 141 μl (0.81 mmol) N,N-diisopropylethylamine and 307 mg (0.81 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 in two portions 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 255 mg (0.22 mmol, 28% of theory) of the desired product.

後処理

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

出典と根拠

ORDレコード
ord-d4dbac289dd94c5981b85fe1d49358bc
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…