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 911988ノート

反応式

HRID 911988 の反応式
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]

参加物

10

反応物 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

生成物 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

試薬・触媒・溶媒 5

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

反応条件

温度
115 °C

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-11c62c2dcd68498e8c9d108a17399930
出典データセット
uspto-grants-2011_09
特許番号
US08022206B2

反応ノート

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