Dichloromethane → tert-butyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473851

반응식

HRID 473851 반응식
Br[C:2]1[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][CH:3]=1.[CH3:11][C:12]([O:15][C:16]([N:18]1[CH2:24][C:23]2[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][C:22]=2[O:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])[CH3:13].ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:8]([NH:7][C:5]1[S:6][C:2]([C:26]2[CH:27]=[CH:28][C:22]3[O:21][CH2:20][CH2:19][N:18]([C:16]([O:15][C:12]([CH3:13])([CH3:11])[CH3:14])=[O:17])[CH2:24][C:23]=3[CH:25]=2)=[CH:3][N:4]=1)(=[O:10])[CH3:9]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 3502602-Acetamido-5-bromo-1,3-thiazoleHCID 59604707(4-(Tert-butoxycarbonyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acid

생성물 1

HCID 59604271tert-butyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate수율 56.2%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
93 °C

실험 절차

A mixture of N-(5-bromothiazol-2-yl)acetamide (1.00 g, 4.52 mmol), (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (1.54 g, 5.43 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.33 g, 0.40 mmol), potassium carbonate (2.50 g, 18.1 mmol) in 1,4-dioxane (20 mL) and water (2 mL) was degassed with nitrogen for 5 minutes and then stirred at 93° C. for 18 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (80 mL), filtered over celite. The filtrate was washed with brine (2×50 mL), dried over sodium sulfate, filtered, concentrated. The residue was purified by flash chromatography (20% to 80% ethyl acetate-hexane gradient) to give 1,1-dimethylethyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.99 g, 2.54 mmol, 56.2% yield); MS (EI) for C19H23N3O4S: 390 (MH+).

후처리

  1. customwas degassed with nitrogen for 5 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (80 mL)
  4. filtrationfiltered over celite
  5. washThe filtrate was washed with brine (2×50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (20% to 80% ethyl acetate-hexane gradient)

출처 및 근거

ORD 기록
ord-63d30e9f795d42558277dcbf79bf0050
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637499B2

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