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 630667노트

반응식

HRID 630667 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d4dbac289dd94c5981b85fe1d49358bc
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315543B2

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