Hexylene Glycol → (s)-Tert-butyl 4-((e)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((r)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate

HRID 417822

반응식

HRID 417822 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[O:18][C:17]3[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:16]=3[N:15]=2)[CH2:10][C@@H:9]1[CH2:30][C:31]([OH:33])=[O:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.[CH3:46][CH:47](O)[CH2:48][C:49]([OH:52])([CH3:51])[CH3:50]>CN(C=O)C.CN(C)C1C=CN=CC=1>[Cl:29][C:27]1[CH:26]=[CH:25][C:17]2[O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C@@H:9]([CH2:30][C:31]([O:33][C@@H:47]([CH2:48][C:49]([OH:52])([CH3:51])[CH3:50])[CH3:46])=[O:32])[CH2:10]3)=[N:15][C:16]=2[CH:28]=1

참가 물질

6

반응물 3

HCID 7870Hexylene GlycolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59822173(s)-2-(1-(Tert-butoxycarbonyl)-4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid

생성물 1

HCID 59822183(s)-Tert-butyl 4-((e)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((r)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

(S)-2-(1-(tert-butoxycarbonyl)-4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid (288 mg, 0.61 mmol) can be dissolved in DMF (5 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (222 mg, 1.16 mmol), and 4-Dimethylaminopyridine (48 mg, 0.39 mmol) can be added respectively at room temperature under nitrogen. After about fifteen minutes R-(−)-2-Methyl-2,4-pentanediol (92 mg, 0.78 mmol) can be added and the mixture should be heated to about 50 C under nitrogen. The product can be purified by flash chromatography using 10% Acetone/Dichloromethane as the eluent to give (S)-tert-butyl 4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((R)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate. (S)-tert-butyl 4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((R)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate can be dissolved in dichloromethane (1.1 ml) and cooled in an ice bath. Trifluoroacetic acid (0.5 ml) should be added drop wise under nitrogen and slowly allowed to reach room temperature while running overnight. The mixture should be concentrated under vacuum and purified by flash chromatography using 10% Acetone/Dichloromethane as the eluent to give Compound ED.

후처리

  1. temperaturethe mixture should be heated to about 50 C under nitrogen
  2. customThe product can be purified by flash chromatography

출처 및 근거

ORD 기록
ord-5e709edaa0fe47aea397db0e2f228676
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093237B2

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