Sodium Carbonate → HCID 67470542, compound

HRID 407901Notes

Reaction equation

HRID 407901 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][C:21]=4[F:30])[C:15]3=[O:31])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[N:42][N:43](C(OC(C)(C)C)=O)[CH:44]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[NH:42]1[CH:41]=[C:40]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]4[CH2:18][CH2:17][C@H:16]([NH:19][C:20]5[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][C:21]=5[F:30])[C:15]4=[O:31])[CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH:44]=[N:43]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 67469823HCID 67469823, compound

Product 1

HCID 67470542HCID 67470542, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(S)-1-(1-(5-Bromopyrimidin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (Example 7; 0.090 g, 0.17 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.057 g, 0.19 mmol), Pd(PPh3)4 (0.020 g, 0.018 mmol) and Na2CO3 (0.44 mL, 0.88 mmol) were suspended in dioxane in a sealed tube and stirred at 110° C. overnight. The material was cooled and filtered through silica gel (10% MeOH/EtOAc). The material was purified by reverse phase HPLC purification (5 to 95% acetonitrile in water) to give (S)-1-(1-(5-(1H-pyrazol-4-yl)pyrimidin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.037 g, 42% yield) as a white solid. Mass spectrum (apci) m/z=500.3 (M+H).

Workup

  1. temperatureThe material was cooled
  2. filtrationfiltered through silica gel (10% MeOH/EtOAc)
  3. customThe material was purified by reverse phase HPLC purification (5 to 95% acetonitrile in water)

Sources & evidence

ORD record
ord-138a2253bc42495ab12b2ddcc7162f7a
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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