1,2-Dichloroethane → (R)-1-(3-(ethylamino)-7-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

HRID 590833Notes

Reaction equation

HRID 590833 reaction equation
[CH2:1]([NH:3][C:4]1[C:8]2[CH:9]=[N:10][C:11]([NH:13][C:14]([NH:16][C@@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])=[O:15])=[CH:12][C:7]=2[NH:6][N:5]=1)[CH3:2].[F:25][C:26]([F:31])([F:30])S([O-])=O.[Na+].ClCCCl.C(OO)(C)(C)C>CS(C)=O.O>[CH2:1]([NH:3][C:4]1[C:8]2[CH:9]=[N:10][C:11]([NH:13][C:14]([NH:16][C@@H:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:18])=[O:15])=[C:12]([C:26]([F:31])([F:30])[F:25])[C:7]=2[NH:6][N:5]=1)[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 6410tert-Butyl hydroperoxideHCID 23690734Sodium trifluoromethanesulfinateHCID 73504570(R)-1-(3-(ethylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Product 1

HCID 73505225(R)-1-(3-(ethylamino)-7-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

(R)-1-(3-(ethylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (50 mg, 0.154 mmol) and sodium trifluoromethanesulfinate (72.2 mg, 0.462 mmol) were taken in a solvent mixture containing DCE:water:DMSO in a ratio of 2.5:1:0.5, cooled to 0° C. and added tert-butyl hydroperoxide (0.107 mL, 0.771 mmol) and reaction gradually warmed to room temperature. After two more additions of tert-butyl hydroperoxide in equal concentrations in a span of 36 hours, the reaction was partitioned between DCM and aqueous sodium bicarbonate. The organics were washed with brine, dried with sodium sulfate and concentrated. Purification of residue by flash column (0-15% MeOH-DCM) gave (R)-1-(3-(ethylamino)-7-(trifluoromethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI [M+H]+ calc'd. 393. found 393. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 8.60 (s, 1H), 7.40-7.30 (m, 4H), 7.20 (m, 1H), 7.10 (s, 1H), 4.97 (m, 1H), 3.29, (m, 2H), 1.38 (d, J=6.5 Hz, 3H), 1.25 (t, J=7.0 Hz, 3H).

Workup

  1. additionadded
  2. concentrationAfter two more additions of tert-butyl hydroperoxide in equal concentrations in a span of 36 hours
  3. customthe reaction was partitioned between DCM and aqueous sodium bicarbonate
  4. washThe organics were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customPurification of residue by flash column (0-15% MeOH-DCM)

Sources & evidence

ORD record
ord-8131940520b5450d9fc5afdb660029ed
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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