2-(Dicyclohexylphosphino)biphenyl → 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-ol

HRID 2040949Notes

Reaction equation

HRID 2040949 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([N:9]3[CH2:12][CH:11]([OH:13])[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:16][N:17]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[N:18]1.C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1.C(O)C>[CH3:16][N:17]1[CH:21]=[C:20]([C:2]2[CH:15]=[CH:14][C:5]3[N:6]=[C:7]([N:9]4[CH2:12][CH:11]([OH:13])[CH2:10]4)[S:8][C:4]=3[CH:3]=2)[CH:19]=[N:18]1

Participants

6

Reactant 3

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 669060671-(6-Bromobenzo[d]thiazol-2-yl)azetidin-3-ol

Product 1

HCID 669055801-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-ol

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 22560076Dioxan ethanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-(6-bromobenzo[d]thiazol-2-yl)azetidin-3-ol (Reference Example 1, 1.426 g, 5.0 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CAS #761446-44-0, 1.248 g, 6.0 mmol), dichlorobis(triphenylphosphine)palladium (II) (0.140 g, 0.20 mmol), and (2-biphenyl)dicyclohexylphosphine (0.070 g, 0.20 mmol) in 1:1 dioxane/ethanol (12 mL) was treated with deoxygenated 1 M aqueous Na2CO3 (6.0 mL). The reaction mixture was then heated under microwave irradiation at 150° C. for 10 minutes. The reaction mixture was then diluted with dichloromethane (30 mL) and filtered through a pad of diatomaceous earth that was subsequently rinsed with 9:1 dichloromethane/methanol. The filtrate was concentrated under reduced pressure and the residue was treated with acetonitrile (20 mL) to provide a slurry that was filtered. The filter cake was treated with 4:1 methanol/water (5 mL) and the resulting slurry was filtered. The filter cake was rinsed with 4:1 methanol/water (3 mL), then dried under vacuum to provide 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-ol. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.82-3.91 (m, 2H), 3.85 (s, 3H), 4.31 (t, J=8 Hz, 2H), 4.62-4.72 (m, 1H), 5.86-5.91 (m, 1H), 7.43 (d, J=8 Hz, 1H), 7.48 (dd, J=1, 8 Hz, 1H), 7.82 (d, J=1 Hz, 1H), 7.96 (d, J=1 Hz, 1H), 8.07 (s, 1H); MS (DCI/NH3) m/z 287 (M+H)+.

Workup

  1. additionwas treated
  2. customwith deoxygenated 1 M aqueous Na2CO3 (6.0 mL)
  3. additionThe reaction mixture was then diluted with dichloromethane (30 mL)
  4. filtrationfiltered through a pad of diatomaceous earth that
  5. washwas subsequently rinsed with 9:1 dichloromethane/methanol
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additionthe residue was treated with acetonitrile (20 mL)
  8. customto provide a slurry that
  9. filtrationwas filtered
  10. additionThe filter cake was treated with 4:1 methanol/water (5 mL)
  11. filtrationthe resulting slurry was filtered
  12. washThe filter cake was rinsed with 4:1 methanol/water (3 mL)
  13. customdried under vacuum

Sources & evidence

ORD record
ord-3c942b78b6b846738f5c71cde9bdcb1d
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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