Tricyclohexylphosphine → HCID 68754973, compound

HRID 2046412Notes

Reaction equation

HRID 2046412 reaction equation
Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH:11]1[C:23]2[CH:22]([CH2:24][O:25][C:26](=[O:55])[NH:27][C@H:28]3[CH2:33][CH2:32][CH2:31][C:30]([F:35])([F:34])[C@@H:29]3[NH:36][C:37]([C:39]3[S:40][C:41]([CH2:53][CH3:54])=[C:42](B4OC(C)(C)C(C)(C)O4)[CH:43]=3)=[O:38])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+]>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].O1CCOCC1>[CH:11]1[C:23]2[CH:22]([CH2:24][O:25][C:26](=[O:55])[NH:27][C@H:28]3[CH2:33][CH2:32][CH2:31][C:30]([F:35])([F:34])[C@@H:29]3[NH:36][C:37]([C:39]3[S:40][C:41]([CH2:53][CH3:54])=[C:42]([C:2]4[N:6]5[N:7]=[CH:8][CH:9]=[CH:10][C:5]5=[N:4][CH:3]=4)[CH:43]=3)=[O:38])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 75806Tricyclohexylphosphine2×HCID 517044Potassium Acetate2×HCID 128723193-Bromoimidazo(1,2-b)pyridazineHCID 67145207HCID 67145207, compound2×

Product 1

HCID 68754973HCID 68754973, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-Bromoimidazo[1,2-b]pyridazine (53 mg, 0.27 mmol), 9H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate (187 mg, 0.294 mmol), Pd2(dba)3 (25 mg, 0.03 mmol), tricyclohexylphosphine (19 mg, 0.07 mmol), and aqueous tribasic potassium acetate (0.71 mL, 0.91 mmol, 1.27 M) were placed into a sealed tube and 1,4-dioxane (5.4 mL) added. The sealed tube was purged with nitrogen for 5 minutes and heated at 100° C. for 18 h. The solution was cooled to room temperature and additional 9H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate (85 mg, 0.13 mmol), Pd2(dba)3 (12 mg, 0.01 mmol), tricyclohexylphosphine (8 mg, 0.03 mmol), and aqueous tribasic potassium acetate (0.42 mL, 0.54 mmol, 1.27 M) were added. The sealed tube was purged with nitrogen for 5 minutes and heat at 100° C. for 4 h. The solution was then cooled to room temperature and quenched with aqueous saturated sodium bicarbonate and extracted with dichloromethane (×3). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was taken on to the deprotection step without purification. LRMS (APCI) calc'd for (C34H31F2N5O3S) [M+H]+, 628.2. found 628.2.

Workup

  1. customThe sealed tube was purged with nitrogen for 5 minutes
  2. temperatureThe solution was cooled to room temperature
  3. customThe sealed tube was purged with nitrogen for 5 minutes
  4. temperatureheat at 100° C. for 4 h
  5. temperatureThe solution was then cooled to room temperature
  6. customquenched with aqueous saturated sodium bicarbonate
  7. extractionextracted with dichloromethane (×3)
  8. dry with materialThe combined organic layers were dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was taken on to the deprotection step without purification

Sources & evidence

ORD record
ord-f03acc71d9204e25af79ca5d2459c025
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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