Potassium Carbonate → HCID 178449968, compound

HRID 1484988Notes

Reaction equation

HRID 1484988 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([Cl:13])=[C:11]([CH:14]2[CH2:16][CH2:15]2)[N:10]=[C:9]([C:17]2[S:18][C:19]([S:22](=[O:29])(=[O:28])[NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][CH:21]=2)[N:8]=1)(=O)=O.[NH2:32][C:33]1[N:37](C(OC(C)(C)C)=O)[N:36]=[C:35]([CH:45]2[CH2:47][CH2:46]2)[CH:34]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[C:24]([NH:23][S:22]([C:19]1[S:18][C:17]([C:9]2[N:10]=[C:11]([CH:14]3[CH2:16][CH2:15]3)[C:12]([Cl:13])=[C:7]([NH:32][C:33]3[NH:37][N:36]=[C:35]([CH:45]4[CH2:47][CH2:46]4)[CH:34]=3)[N:8]=2)=[CH:21][CH:20]=1)(=[O:28])=[O:29])([CH3:26])([CH3:25])[CH3:27]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 11356513tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylateHCID 58169345HCID 58169345, compound

Product 1

HCID 178449968HCID 178449968, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(5-(N-tert-butylsulfamoyl)thiophen-2-yl)-5-chloro-6-cyclopropylpyrimidin-4-yl trifluoromethane sulfonate (200 mg, 0.38 mmol, 1.0 eq), tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate (129 mg, 0.58 mmol, 1.2 eq), Ph3P (30 mg, 0.11 mmol, 0.3 eq), Ph(Ph3P)4 (44 mg, 0.038 mmol, 0.1 eq) and K2CO3 (158 mg, 1.14 mmol, 3 eq) in dioxane (5 mL) was stirred at 100° C. for 3 h. The mixture was extracted with EtOAc. The combined organic phases were washed (brine), dried (Na2SO4), filtered and concentrated to give a residue, which was purified by silica gel column chromatography (PE/EtOAc/MeOH=1:1:0.1) to provide N-tert-butyl-5-(5-chloro-4-cyclopropyl-6-(3-cyclopropyl-1H-pyrazol-5-ylamino)pyrimidin-2-yl)thiophene-2-sulfonamide (60 mg, 32%) as a white solid. LC-MS (m/z)=493.9 [M+H]+

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washThe combined organic phases were washed (brine)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue, which
  7. customwas purified by silica gel column chromatography (PE/EtOAc/MeOH=1:1:0.1)

Sources & evidence

ORD record
ord-860f9d14e1004060906c720bc2b9b26b
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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