Nitrogen → 3-(1-tert-Butyl-1,2,3,6-tetrahydropyridin-4-yl)-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-amine

HRID 911988노트

반응식

HRID 911988 반응식
N#N.[Cl:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([Cl:11])[C:5]=1[C@H:12]([O:14][C:15]1[C:16]2[O:24][CH:23]=[C:22](Br)[C:17]=2[CH:18]=[N:19][C:20]=1[NH2:21])[CH3:13].[C:26]([N:30]1[CH2:35][CH:34]=[C:33]([Sn](C)(C)C)[CH2:32][CH2:31]1)([CH3:29])([CH3:28])[CH3:27].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO.C(N(CC)CC)C.CN(C=O)C>[C:26]([N:30]1[CH2:31][CH:32]=[C:33]([C:22]2[C:17]3[CH:18]=[N:19][C:20]([NH2:21])=[C:15]([O:14][C@@H:12]([C:5]4[C:6]([Cl:11])=[CH:7][CH:8]=[C:9]([F:10])[C:4]=4[Cl:3])[CH3:13])[C:16]=3[O:24][CH:23]=2)[CH2:34][CH2:35]1)([CH3:29])([CH3:28])[CH3:27]

참가 물질

10

반응물 4

HCID 947NitrogenHCID 80271Tri-o-tolylphosphineHCID 226481771-Tert-butyl-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridineHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

생성물 1

HCID 578125743-(1-tert-Butyl-1,2,3,6-tetrahydropyridin-4-yl)-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-amine

시약·촉매·용매 5

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

반응 조건

온도
115 °C

실험 절차

In a two necked RB flask (50 mL), equipped with a N2 in let, a water condenser, and a magnetic stirrer, were placed 7-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-3-bromofuro[3,2-c]pyridine-6-amine (230 mg, 0.55 mmol), 1-tert-Butyl-1,2,3,6-tetrahydro-4-(trimethylstannyl)pyridine (240 mg, 0.79 mmol), tris(dibenzylideneacetone)dipalladium(0) (100 mg), tri-O-tolylphosphine (26 mg), DMF (10 mL) and triethylamine (1.0 mL). This reaction mixture was heated at 114-116° C. for 4 h. The TLC (10% MeOH in DCM) indicated that the starting material was consumed. From the reaction mixture DMF was removed under reduced pressure, water was added to the residue, and the mixture was extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was purified on silica gel column chromatography eluting with 2-5% methanol in dichloromethane to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=1.19 (s, 9H), 1.81 (d, J=6.6 Hz, 3H), 2.42 (br, m, 2H), 2.80 (m, 2H), 3.40 (br, m, 2H), 4.75 (br, 2H), 6.22 (br, 1H), 6.50 (m, 1H), 7.05 (t, J=8.4 Hz, 1H), 7.25 (m, J=8.4 Hz, 1H), 7.34 (s, 1H), 8.23 (s, 1H). EI-MS 478/480 (MH+).

후처리

  1. customa water condenser, and a magnetic stirrer, were placed
  2. customwas consumed
  3. customFrom the reaction mixture DMF was removed under reduced pressure, water
  4. additionwas added to the residue
  5. extractionthe mixture was extracted with DCM
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified on silica gel column chromatography
  10. washeluting with 2-5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-11c62c2dcd68498e8c9d108a17399930
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022206B2

반응 노트

불러오는 중…