1,2-Dimethoxyethane → 5-[(4-fluoro-1-methylpiperidin-4-yl)carbonyl]-N-(5-fluoro-2-vinylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine

HRID 331073

Reaction equation

HRID 331073 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:10]3[CH2:16][N:15]([C:17]([C:19]4([F:26])[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]4)=[O:18])[C:14]([CH3:28])([CH3:27])[C:11]=3[NH:12][N:13]=2)[C:5]([F:29])=[CH:4][N:3]=1.[CH3:30][C:31]1(C)C(C)(C)OB(C=C)O1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O>[F:26][C:19]1([C:17]([N:15]2[CH2:16][C:10]3[C:9]([NH:8][C:6]4[C:5]([F:29])=[CH:4][N:3]=[C:2]([CH:30]=[CH2:31])[N:7]=4)=[N:13][NH:12][C:11]=3[C:14]2([CH3:28])[CH3:27])=[O:18])[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 59333922[3-(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-6,6-dimethyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl]-(4-fluoro-1-methyl-piperidin-4-yl)-methanone

Product 1

HCID 593340165-[(4-fluoro-1-methylpiperidin-4-yl)carbonyl]-N-(5-fluoro-2-vinylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a pressure vessel was added starting material [3-(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-6,6-dimethyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl]-(4-fluoro-1-methyl-piperidin-4-yl)-methanone (0.375 g, 0.881 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2 dioxaborolane (0.407 g, 2.64 mmol), Na2CO3 (0.280 g, 2.64 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.144 g, 0.176 mmol) followed by DME (10 mL) and water (2 mL). The reaction mixture was purged with argon for 2 min, then heat to 100° C. for 15 h. The volatiles were concentrated in vacuo and the residue redissolved in EtOAc (15 mL). The organic layer was washed with water (10 mL), dried over MgSO4, filtered, and concentrated to give the desired product G1(i) as a brown foam (0.35 g, 95%). Mass Spectrum: Calcd for C20H26N7OF2 (M+H): 418. Found: 418.

Workup

  1. additionTo a pressure vessel was added
  2. customThe reaction mixture was purged with argon for 2 min
  3. concentrationThe volatiles were concentrated in vacuo
  4. dissolutionthe residue redissolved in EtOAc (15 mL)
  5. washThe organic layer was washed with water (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8d93b933d4c24472b792407d57d3540a
Source dataset
uspto-grants-2014_11
Patent number
US08877761B2

Linked notes

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