Diisopropylethylamine → 3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670579노트

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HRID 1670579 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][SH:21])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:23]1[N:28]=[CH:27][C:26]([C:29]2[N:30]=[C:31]([NH:34][CH2:35][CH:36]3[CH2:38][CH2:37]3)[S:32][CH:33]=2)=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:23]3[CH:24]=[CH:25][C:26]([C:29]4[N:30]=[C:31]([NH:34][CH2:35][CH:36]5[CH2:37][CH2:38]5)[S:32][CH:33]=4)=[CH:27][N:28]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 59822270HCID 59822270, 화합물HCID 598222763-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

생성물 1

HCID 866237113-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 94%

시약·촉매·용매 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.078 g, 0.239 mmol) in anhydrous dioxane (1.1 mL), add N-[4-(6-bromo-pyridin-3-yl)-thiazol-2-yl]-cyclopropylmethylamine (0.067 g, 0.218 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.0055 mmol), Xantphos (6.3 mg, 0.011 mmol) and diisopropylethylamine (0.076 mL, 0.44 mmol) at room temperature. Purge the reaction mixture with nitrogen and heat the mixture at 100° C. overnight. Cool the reaction mixture to room temperature. Dilute with DCM (50 mL) and filter through Celite®. Concentrate the filtrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.113 g, 94%) as a pale yellow foam. MS (ES+) m/z: 557.2 (M+H)+.

후처리

  1. customPurge the reaction mixture with nitrogen
  2. temperatureCool the reaction mixture to room temperature
  3. additionDilute with DCM (50 mL)
  4. filtrationfilter through Celite®
  5. concentrationConcentrate the filtrate in vacuo
  6. dissolutionDissolve the residue in DCM
  7. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min)

출처 및 근거

ORD 기록
ord-a8bf0549c3ad47a99fe64aa3bfa48945
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994163B2

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