methyl cis-5-amino-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate → methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylate

HRID 383787Notes

Reaction equation

HRID 383787 reaction equation
[NH2:1][C@H:2]1[CH2:7][N:6]([C:8]2[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([NH:15][C:16]3[NH:20][N:19]=[CH:18][CH:17]=3)[N:9]=2)[CH2:5][C@@H:4]([C:21]([O:23][CH3:24])=[O:22])[CH2:3]1.[C:25](=O)([O:36][C@@H:37]([CH3:42])[C:38]([F:41])([F:40])[F:39])[O:26]C1C=CC([N+]([O-])=O)=CC=1>C(Cl)(Cl)Cl.CCN(C(C)C)C(C)C>[CH3:14][C:12]1[CH:11]=[C:10]([NH:15][C:16]2[NH:20][N:19]=[CH:18][CH:17]=2)[N:9]=[C:8]([N:6]2[CH2:7][C@H:2]([NH:1][C:25]([O:36][C@@H:37]([CH3:42])[C:38]([F:41])([F:40])[F:39])=[O:26])[CH2:3][C@H:4]([C:21]([O:23][CH3:24])=[O:22])[CH2:5]2)[N:13]=1

Participants

5

Reactant 2

HCID 66660299methyl cis-5-amino-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylateHCID 687562104-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonate

Product 1

HCID 66660365methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

The crude methyl cis-5-amino-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate prepared in Step 4 of Example 6 was dissolved into CHCl3 (6 ml). To the solution was added the solution of 4-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonate (203.3 mg) in CHCl3 and DIEA (125.0 μl). After stirring at room temperature for 2 hours, the mixture was concentrated in vacuo. The residue was dissolved into EtOAc, poured into 1 M aqueous solution of NaOH and extracted with EtOAc. The extract was washed with saturated aqueous solution of NaHCO3, dried over MgSO4 and concentrated to give the crude methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylate as a pale orange amorphous form.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved into EtOAc
  3. additionpoured into 1 M aqueous solution of NaOH
  4. extractionextracted with EtOAc
  5. washThe extract was washed with saturated aqueous solution of NaHCO3
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b62ddfc14584401a9dc0248dfca81268
Source dataset
uspto-grants-2013_02
Patent number
US08367690B2

Reaction notes

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