Cesium carbonate → 6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)bicyclo[3.1.0]hexan-2-ol

HRID 2203672Notes

Reaction equation

I[C:2]1[CH:6]=[C:5]([CH:7]2[CH:12]3[CH:8]2[CH2:9][CH2:10][CH:11]3[OH:13])[N:4]([CH:14]([CH3:16])[CH3:15])[N:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]([C:32]([F:35])([F:34])[F:33])[C:28]([NH2:31])=[N:29][CH:30]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[NH2:31][C:28]1[N:29]=[CH:30][C:25]([C:2]2[CH:6]=[C:5]([CH:7]3[CH:12]4[CH:8]3[CH2:9][CH2:10][CH:11]4[OH:13])[N:4]([CH:14]([CH3:16])[CH3:15])[N:3]=2)=[CH:26][C:27]=1[C:32]([F:35])([F:33])[F:34]

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of (±)-6-(3-iodo-1-isopropyl-1H-pyrazol-5-yl)bicyclo[3.1.0]hexan-2-ol (30 mg, 90.3 μmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine (39 mg, 0.14 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (6 mg, 0.009 mmol) and cesium carbonate (59 mg, 0.18 mmol) in 1,4-dioxane (0.5 mL) and water (0.1 mL) was purged with nitrogen. The reaction mixture was heated to 110° C. by microwave irradiation for 20 min. The mixture was concentrated, and the resulting residue was diluted with ethyl acetate (2 mL), and the solution was filtered. The filtrate was concentrated. Purification by preparation HPLC followed by chiral SFC separation afforded the title compounds:

Workup

concentrationThe mixture was concentrated
additionthe resulting residue was diluted with ethyl acetate (2 mL)
filtrationthe solution was filtered
concentrationThe filtrate was concentrated
customPurification
customby preparation HPLC
customfollowed by chiral SFC separation

Sources & evidence

ORD record: ord-b1a57cdd1fa34c70ab3e971a8262add2
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365583B2

Reaction notes

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