Ethanol → HCID 69264431, compound

HRID 1484735Notes

Reaction equation

HRID 1484735 reaction equation
[CH:1]1(B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Br[C:14]1[C:18]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][N:16]([C:27]2[CH:28]=[N:29][CH:30]=[C:31]([F:33])[CH:32]=2)[N:15]=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:1]1([C:14]2[C:18]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][N:16]([C:27]3[CH:28]=[N:29][CH:30]=[C:31]([F:33])[CH:32]=3)[N:15]=2)[CH2:3][CH2:2]1.[F:33][C:31]1[CH:32]=[C:27]([N:16]2[CH:17]=[C:18]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH:14]=[N:15]2)[CH:28]=[N:29][CH:30]=1

Participants

9

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86664682HCID 86664682, compound

Product 2

HCID 69264431HCID 69264431, compoundYield 71.9%HCID 69264432HCID 69264432, compoundYield 28.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.087 g, 6.47 mmol) in toluene (13.69 ml) was added tert-butyl (3-bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (1.1 g, 3.08 mmol) followed by ethanol (6.84 ml) and 2 M aqueous potassium carbonate (3.08 mL, 6.16 mmol). The solution was degassed by applying vacuum and then purging with nitrogen (3 times). To the reaction mixture was added palladium tetrakis (0.178 g, 0.154 mmol) and the flask was heated at 100° C. under nitrogen for 36 hours. Water (5 mL) was added and the mixture was extracted with ethyl acetate. The combined organics were concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give tert-butyl (3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (705 mg, 2.215 mmol, 71.9% yield) as a yellow solid and tert-butyl (1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (242 mg, 0.870 mmol, 28.2% yield) as a yellow solid. tert-Butyl (3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 156.5-158.0; 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 8.30 (d, J=2.5 Hz, 1H), 8.27 (s, 1H), 7.76 (dt, J=9.8, 2.4 Hz, 1H), 6.43 (s, 1H), 1.55 (s, 9H), 1.01-0.91 (m, 4H); ESIMS m/z 319 ([M+H]+).

Workup

  1. customThe solution was degassed
  2. custompurging with nitrogen (3 times)
  3. extractionthe mixture was extracted with ethyl acetate
  4. concentrationThe combined organics were concentrated
  5. customchromatographed (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-847558ebc87046249f0f909ce07ac121
Source dataset
uspto-grants-2016_08
Patent number
US09422278B2

Reaction notes

Loading…