Cesium carbonate → HCID 59706185, compound

HRID 1360132Notes

Reaction equation

HRID 1360132 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([N:22]2[CH2:26][CH2:25][C:24]([F:28])([F:27])[CH2:23]2)[CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1.C(=O)(OC(C)(C)C)[NH2:30].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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]>[F:27][C:24]1([F:28])[CH2:25][CH2:26][N:22]([CH:8]([C:4]2[N:3]=[C:2]([NH2:30])[CH:7]=[CH:6][CH:5]=2)[CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH2:23]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57425785HCID 57425785, compound

Product 1

HCID 59706185HCID 59706185, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The 2-bromo-6-[1-(3,3-difluoropyrrolidin-1-yl)-2,2-dipyridin-3-ylethyl]pyridine (73 mg, 0.16 mmol), tert-butyl carbamate (23 mg, 0.2 mmol), Cs2CO3 (75 mg, 0.23 mmol), Pd2(dba)3 (3 mg, 0.003 mmol), and xantphos (6 mg, 0.01 mmol) were combined in dry 1,4-dioxane (1.5 mL). The mixture was degassed (3× pump/N2) then heated to 100° C. After 5 hr the mixture was cooled to RT, diluted with EtOAc, filtered through a pad of Celite, and concentrated. The residue was taken up in 1 mL CH2Cl2 to which was added 1 mL TFA at RT. After 90 min the mixture was concentrated. The residue was taken up in saturated NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column (gradient, 0-10% MeOH/CH2Cl2) gave the title compound as a yellow foam. 1H-NMR (500 MHz, CDCl3) δ 8.68 (d, J=2.20 Hz, 1 H), 8.47 (d, J=4.15 Hz, 1 H), 8.37 (d, J=2.19 Hz, 1 H), 8.25 (d, J=3.90 Hz, 1 H), 7.74 (d, J=8.06 Hz, 1 H), 7.41 (d, J=7.81 Hz, 1 H), 7.25 (m, 2 H), 7.02 (m 1 H), 6.27 (m, 2 H), 4.85 (d, J=11.47 Hz, 1 H), 4.39 (s, 2 H), 4.35 (d, J=11.72 Hz, 1 H), 3.10 (m, 1 H), 2.86 (m, 2 H), 2.67 (m, 1 H), 2.0 (m, 2 H); MS (M+H)+ 382.0.

Workup

  1. customThe mixture was degassed (3× pump/N2)
  2. temperatureAfter 5 hr the mixture was cooled to RT
  3. additiondiluted with EtOAc
  4. filtrationfiltered through a pad of Celite
  5. concentrationconcentrated
  6. additionwas added 1 mL TFA at RT
  7. concentrationAfter 90 min the mixture was concentrated
  8. extractionextracted with CH2Cl2 (3×)
  9. dry with materialThe combined organic layers were dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-cd1d9b3f3e714952942bd48682728fba
Source dataset
uspto-grants-2011_02
Patent number
US07879839B2

Reaction notes

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