Sodium Carbonate → (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500718Notes

Reaction equation

HRID 500718 reaction equation
I[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)=[CH:5][N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=1.[CH3:21][NH:22][C:23]1[C:28]([CH3:29])=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[CH:18]([N:4]1[CH:5]=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)[C:2]([C:26]2[CH:25]=[N:24][C:23]([NH:22][CH3:21])=[C:28]([CH3:29])[CH:27]=2)=[N:3]1)([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 57416512N,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-amineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

Product 1

HCID 25181760(2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-olYield 17%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-1-3) (1 g, 2.58 mmol) in toluene (30 mL) and EtOH (10 mL) were added N,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (B-4-3) (2 g, 6.3 mmol in theory) and 2 N aq. Na2CO3 (4 mL). The resulting mixture was degassed under N2 for 2 minutes. Then Pd(PPh3)4 (0.3 g, 0.26 mmol) was added and the mixture was degassed again. The reaction was heated to 80-90° C. and stirred overnight. MS showed the reaction was complete and the mixture was cooled. The organic layer was separated and concentrated. The residue was purified by prep. HPLC to afford (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-4) (0.167 g, 16.98%) as a light yellow solid.

Workup

  1. customThe resulting mixture was degassed under N2 for 2 minutes
  2. customthe mixture was degassed again
  3. temperaturethe mixture was cooled
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customThe residue was purified by prep

Sources & evidence

ORD record
ord-fe1c12ddddec40f6a097625b6a29b2db
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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