Potassium Carbonate → 9-tert-butyl-2-(3-pyridyl)-14-(3,6-dihydro-2H-pyran-4-yl)-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971756노트

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HRID 1971756 반응식
[C:1]([N:5]1[CH2:32][CH2:31][CH2:30][CH2:29][C:8]2[C:9](Br)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:33])([CH3:4])([CH3:3])[CH3:2].[O:34]1[CH2:39][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH2:36][CH2:35]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:5]1[CH2:32][CH2:31][CH2:30][CH2:29][C:8]2[C:9]([C:37]3[CH2:38][CH2:39][O:34][CH2:35][CH:36]=3)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:33])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 581248489-tert-butyl-2-(3-pyridyl)-14-bromo-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

생성물 1

HCID 581249569-tert-butyl-2-(3-pyridyl)-14-(3,6-dihydro-2H-pyran-4-yl)-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
125 °C

실험 절차

A mixture of 75 mg of 25b, 37 mg of 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5,-tetramethyl-1,3,2-dioxaborolane, 41 mg of K2CO3 and 17 mg of tetrakis(triphenylphosphine)palladium(0) in 3 ml of degassed DMF was heated under N2 atmosphere at 125° C. for 2 hr. The reaction was cooled and diluted with 15 ml of water. The product was extracted with ethyl acetate. The organic extract was washed with water, dried and concentrated. The remainder was chromatographed over silcagel (using a gradient of heptane/acetone as eluent). The product isolated was triturated with diethyl ether, providing 57 mg of white crystalline 25c; Mp 208-210° C. LC-MS-ESI: [M+1] 512.13. NMR (CDCl3) δ 8.70, 8.58, 7.88, and 7.37 (4×m, 4, pyridine-H), 7.68 and 6.87 (2×s, 2, Ar—H), 1.60 (s, 9, tertC4H9), 3.87 (s, 3, OCH3), 5.75 (m, 1, CH), 4.30 (m, 2, CH2O), 4.70 (bm, 1, CH2), 3.55 (bm, 1, CH), 3.85 (bm, 4, 2×CH2) 3.00 and 3.20 (2×bm, 2, CH2), 2.63 (bm, 2, CH2), 2.35 (m, 2, CH2), 1.70-2.05 (bm, 4, 2×CH2).

후처리

  1. temperatureThe reaction was cooled
  2. extractionThe product was extracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe remainder was chromatographed over silcagel (
  8. customThe product isolated
  9. customwas triturated with diethyl ether

출처 및 근거

ORD 기록
ord-42366e2fb7a544eea4dcccdd3917d0a3
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431564B2

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