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 911988Notes

Reaction equation

HRID 911988 reaction equation
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]

Participants

10

Reactant 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

Product 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

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
115 °C

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-11c62c2dcd68498e8c9d108a17399930
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

Loading…