Nitrogen → tert-Butyl 5-cyclopropyl-3-[(6-{[(1S)-1-(4-fluorophenyl)ethyl]amino}pyridin-2-yl)amino]-1H-pyrazole-1-carboxylate

HRID 2189887Notes

Reaction equation

HRID 2189887 reaction equation
C1(C2C=CC=CC=2)C=CC=CC=1C(P(C)C)P(C)C.CC(C)([O-])C.[Na+].N#N.F[C:29]1[CH:30]=[C:31](CNS(C)(=O)=O)[C:32]([NH:45][C@H:46]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=2)[CH3:47])=[N:33][C:34]=1NC1C=C(OC(C)C)NN=1.[NH2:61][C:62]1[CH:66]=[C:65]([CH:67]2[CH2:69][CH2:68]2)[N:64]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[N:63]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:67]1([C:65]2[N:64]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[N:63]=[C:62]([NH:61][C:34]3[CH:29]=[CH:30][CH:31]=[C:32]([NH:45][C@H:46]([C:48]4[CH:49]=[CH:50][C:51]([F:54])=[CH:52][CH:53]=4)[CH3:47])[N:33]=3)[CH:66]=2)[CH2:69][CH2:68]1

Participants

8

Reactant 5

HCID 947NitrogenHCID 11218347tert-butyl 3-amino-5-cyclopropyl-1H-pyrazole-1-carboxylateHCID 23676156Sodium t-butoxideHCID 86620606(Biphenyl-2-ylmethylene)bis(dimethylphosphine)HCID 178458648HCID 178458648, compound

Product 1

HCID 86620620tert-Butyl 5-cyclopropyl-3-[(6-{[(1S)-1-(4-fluorophenyl)ethyl]amino}pyridin-2-yl)amino]-1H-pyrazole-1-carboxylateYield 36.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 25 ml round bottom flask was added Pd2(dba)3 (84 mg, 0.092 mmol), (biphenyl-2-ylmethylene)bis(dimethylphosphine) (55 mg, 0.184 mmol) and sodium tert-butoxide (132 mg, 1.38 mmol). The flask was sealed and refilled with N2. To the mixture was added a solution of 6-chloro-N-[(1S)-1-(4-fluorophenyl)ethyl]pyridin-2-amine (Method 20; 230 mg, 0.92 mmol) and tert-butyl 3-amino-5-cyclopropyl-1H-pyrazole-1-carboxylate (223 mg, 1.0 mmol) in toluene (4 ml). The reaction mixture was heated at 110° C. overnight. Solvent was removed and EtOAc was added and the mixture was washed with brine and was concentrated. Flash chromatography (15-40% EtOAc in hexanes) gave the title compound (146 mg, 36%). 1H NMR (CDCl3) δ 0.80-1.00 (m, 4H), 1.60 (m, 3H), 1.65 (s, 9H), 1.95 (m, 1H), 4.71 (m, 1H), 4.75 (m, 1H), 5.75 (m, 1H), 6.09 (m, 1H), 6.21 (s, 1H), 7.00 (m, 2H), 7.23 (m, 2H), 7.30 (m, 1H), 9.40 (s, 1H).

Workup

  1. customThe flask was sealed
  2. customSolvent was removed
  3. additionEtOAc was added
  4. washthe mixture was washed with brine
  5. concentrationwas concentrated

Sources & evidence

ORD record
ord-5bb4a4ea6d9645268e21c9728e0b9690
Source dataset
uspto-grants-2012_12
Patent number
US08324252B2

Reaction notes

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