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

HRID 75927Notes

Reaction equation

HRID 75927 reaction equation
C1(C2C=CC=CC=2)C=CC=CC=1C(P(C)C)P(C)C.CC(C)([O-])C.[Na+].N#N.Cl[C:29]1[N:34]=[C:33]([NH:35][C@H:36]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[CH3:37])[CH:32]=[CH:31][CH:30]=1.[NH2:45][C:46]1[CH:50]=[C:49]([CH:51]2[CH2:53][CH2:52]2)[N:48]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[N:47]=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:51]1([C:49]2[N:48]([C:54]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:55])[N:47]=[C:46]([NH:45][C:29]3[CH:30]=[CH:31][CH:32]=[C:33]([NH:35][C@H:36]([C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=4)[CH3:37])[N:34]=3)[CH:50]=2)[CH2:52][CH2:53]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 86620619(S)-6-Chloro-N-[1-(4-fluorophenyl)ethyl]pyridine-2-amine

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-20b852f8ac034966b09415a32e673612
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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