Potassium Carbonate → HCID 117678042, compound

HRID 1778178Notes

Reaction equation

HRID 1778178 reaction equation
[CH:1]12[CH2:6][CH:4]([CH2:5]1)[CH2:3][N:2]2[C:7]1[CH:12]=[C:11]([N:13]2[CH2:18][C@@H:17]3[CH2:19][C@H:14]2[CH2:15][O:16]3)[CH:10]=[C:9](Cl)[N:8]=1.[F:21][CH:22]([F:40])[O:23][C:24]1[C:25]([NH2:39])=[N:26][CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:4]12[CH2:6][CH:1]([CH2:5]1)[N:2]([C:7]1[N:8]=[C:9]([C:28]3[CH:29]=[C:24]([O:23][CH:22]([F:40])[F:21])[C:25]([NH2:39])=[N:26][CH:27]=3)[CH:10]=[C:11]([N:13]3[CH2:18][C@@H:17]4[CH2:19][C@H:14]3[CH2:15][O:16]4)[CH:12]=1)[CH2:3]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 498535313-(difluoroMethoxy)-5-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-aMineHCID 117678064HCID 117678064, compound

Product 1

HCID 117678042HCID 117678042, compoundYield 24.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial charged with (1S,4S)-5-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-chloropyridin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane (70 mg, 0.24 mmol), 3-(difluoromethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (75.53 mg, 0.26 mmol) and potassium carbonate (66.29 mg, 0.48 mmol) in dioxane/water (5:1, 3.0 mL) was added 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (3.5 mg, 0.048 mmol) under nitrogen. The vial was sealed and heated by microwave irradiation at 120° C. for 1 h. The reaction mixture was concentrated in vacuo, and resulting residue was purified by PR-HPLC (Basic) to afford 5-[6-(3-azabicyclo[2.1.1]hexan-3-yl)-4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-pyridyl]-3-(difluoromethoxy)pyridin-2-amine (24.55 mg, 24.6% yield). LCMS (ESI) [MH]+=416.1; 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.91 (s, 1H), 7.15 (t, J=74.0 Hz, 1H), 6.42 (s, 1H), 6.21 (s, 2H), 5.54 (s, 1H), 4.76-4.74 (m, 2H), 4.62 (s, 1H), 3.73 (d, J=6.8 Hz, 1H), 3.63 (d, J=7.6 Hz, 1H), 3.45 (d, J=8.8 Hz, 1H), 3.33 (s, 2H), 3.10 (d, J=10.4 Hz, 1H), 2.88-2.86 (m, 1H), 1.88-1.81 (m, 4H), 1.27-1.26 (m, 2H).

Workup

  1. customThe vial was sealed
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customresulting residue
  4. customwas purified by PR-HPLC (Basic)

Sources & evidence

ORD record
ord-3ecf345b2bb548f2a6ce95f08d0d52f2
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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