Nitrogen → tert-butyl (1E,4E)-4-(dipropylcarbamoyl)-8-(4-hydroxyphenyl)-3H-benzo[b]azepin-2-ylcarbamate

HRID 2275736노트

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HRID 2275736 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:29]=1)[N:7]=[C:8]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9][C:10]([C:12](=[O:20])[N:13]([CH2:17][CH2:18][CH3:19])[CH2:14][CH2:15][CH3:16])=[CH:11]2.[OH:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.CN(C)C(C1C=CC(C2C=CC3=C(C=2)N=C(NC(=O)OC(C)(C)C)CC(C(=O)N(CCC)CCC)=C3)=CC=1)=O.C([O-])([O-])=O.[Na+].[Na+].O.[K].[K].C1(P(C2C=CC(S(O)(=O)=O)=CC=2)C2C=CC(S(O)(=O)=O)=CC=2)C=CC=CC=1.N#N.CN(C)C(C1C=CC(B(O)O)=CC=1)=O>CCO.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH2:14]([N:13]([CH2:17][CH2:18][CH3:19])[C:12]([C:10]1=[CH:11][C:5]2[CH:4]=[CH:3][C:2]([C:34]3[CH:35]=[CH:36][C:31]([OH:30])=[CH:32][CH:33]=3)=[CH:29][C:6]=2[N:7]=[C:8]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9]1)=[O:20])[CH2:15][CH3:16]

참가 물질

11

반응물 7

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 35037674-(Dimethylcarbamoyl)phenylboronic AcidHCID 46928349tert-Butyl (8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-yl)carbamate2회HCID 866526824,4'-(Phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrateHCID 86653475tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate

생성물 1

HCID 86652679tert-butyl (1E,4E)-4-(dipropylcarbamoyl)-8-(4-hydroxyphenyl)-3H-benzo[b]azepin-2-ylcarbamate

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 702Ethanol용매2회HCID 962Water용매

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온도
65 °C

실험 절차

The title compound was prepared by these procedures using tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate and 4-hydroxyphenylboronic acid. Preparation of tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate: To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65° C. with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2). MS APCI (+) m/z 478 (M+1) detected.

후처리

  1. customwas bubbled with N2 for 10 min
  2. customThe resulting mixture was bubbled with N2 for 10 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude material that

출처 및 근거

ORD 기록
ord-06d76da04dd64da1a7146c3094f32b0e
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09126940B2

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