Potassium Carbonate → 3-[1-(2,6-Dichloro-3-fluorophenyl)-ethyl]-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 2046922노트

반응식

HRID 2046922 반응식
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH3:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(OC([N:29]1[CH2:34][CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH2:31][CH2:30]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>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.O1CCOCC1.O>[Cl:21][C:14]1[C:15]([F:20])=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[CH:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:32]3[CH2:33][CH2:34][NH:29][CH2:30][CH:31]=3)[CH:3]=2)[NH:8][CH:9]=1)[CH3:12]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 584314405-Bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 673640813-[1-(2,6-Dichloro-3-fluorophenyl)-ethyl]-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
90 °C

실험 절차

A mixture of 5-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine (60.0 mg, 0.155 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (95.6 mg, 0.309 mmol), Pd(PPh3)4 (40 mg, 0.03 mmol), potassium carbonate (64.1 mg, 0.464 mmol) and 4:1 dioxane/H2O (10 mL) was heated to 90° C. for 2 h. The solution was loaded into an SCX cartridge, washed with MeOH (30 mL) and ejected with 2M NH3 in MeOH (10 mL). The filtrate was concentrated in vacuo, redissolved in dioxane, and 4M HCl in dioxane (1 mL) was added. The solution was heated to 40° C. for 2 h. The material was loaded into an SCX cartridge, washed with MeOH (30 mL) and ejected with 2M NH3 in MeOH (10 mL). The filtrate was concentrated in vacuo, redissolved in MeOH (0.5 mL) and purified via HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=7.3 Hz, 3 H), 2.65-2.73 (m, 2 H), 3.45 (t, J=6.1 Hz, 2 H), 3.76-3.86 (m, 2 H), 5.28 (d, J=7.3 Hz, 1 H), 5.95 (dt, J=3.3, 1.7 Hz, 1 H), 7.19 (t, J=8.6 Hz, 1 H), 7.34 (d, J=2.3 Hz, 1 H), 7.36-7.50 (m, 2 H), 8.26 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 390.00 (100) [MH+]. HPLC: tR=2.48 min (ZQ3, polar—5 min).

후처리

  1. washwashed with MeOH (30 mL)
  2. concentrationThe filtrate was concentrated in vacuo
  3. dissolutionredissolved in dioxane
  4. addition4M HCl in dioxane (1 mL) was added
  5. temperatureThe solution was heated to 40° C. for 2 h
  6. washwashed with MeOH (30 mL)
  7. concentrationThe filtrate was concentrated in vacuo
  8. dissolutionredissolved in MeOH (0.5 mL)
  9. custompurified via HPLC
  10. additionThe fractions containing the pure product
  11. concentrationwere concentrated in vacuo

출처 및 근거

ORD 기록
ord-1f8cd4288e954efc9c6fdbcd52d08cac
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592448B2

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