Potassium Carbonate → (R)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 519139노트

반응식

HRID 519139 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2Br)[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:30])[C:19](=[O:29])[NH:20][N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:37]([O:39]/[CH:40]=[CH:41]/B1OC(C)(C)C(C)(C)O1)[CH3:38]>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(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2/[CH:38]=[CH:37]/[O:39][CH2:40][CH3:41])[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:30])[C:19](=[O:29])[NH:20][N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 86727530(R)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 86727529(R)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester수율 75.2%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a mixture of (R)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.5 g, 0.625 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.05 g, 0.06 mmol) and K2CO3 (0.43 g, 1.87 mmol) in dioxane (24 mL) and water (4 mL) was added 2-((E)-2-ethoxy-vinyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.123 g, 0.62 mmol) and the reaction mixture was stirred at 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether) to give (R)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.22 g, 74%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 6.73 (s, 1H), 6.61 (d, J=12.4 Hz, 1H), 6.07 (s, 1H), 5.56 (d, J=12.4 Hz, 1H), 4.65 (m, 1H), 4.48 (m, 2H), 3.90 (m, 1H), 3.80 (m, 2H), 3.64 (m, 1H), 3.40 (m, 2H), 3.09-3.30 (m, 1H), 2.22 (m, 1H), 1.82 (m, 1H), 1.42 (m, 12H), 1.28 (t, J=7.2 Hz, 3H). LC/MS (Table 1, Method 2) Rt=1.100 min.; MS m/z: 472 [M+H]+. SFC (Table 1, Method 37) Rt=2.183 min.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customto give the crude product, which
  4. customwas purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-93b9e72e75d34f55a559689a3bebdb68
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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