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

HRID 500716Notes

Reaction equation

HRID 500716 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][C:22]1[C:23]([NH2:37])=[N:24][CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=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>[NH2:37][C:23]1[N:24]=[CH:25][C:26]([C:2]2[C:6]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=3)=[CH:5][N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=2)=[CH:27][C:22]=1[CH3:21]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 532167723-Methyl-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 57856319(2S)-1-(4-(3-(6-amino-5-methylpyridin-3-yl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-olYield 11.6%

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) (0.52 g, 1.34 mmol) in toluene (21 mL) and EtOH (7 mL) were added 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (B-3-2) (1 g, 2.68 mmol in theory) and 2 N aq. Na2CO3 (2 mL). The resulting mixture was degassed under N2 for 2 minutes. Then Pd(PPh3)4 (0.15 g, 0.134 mmol) was added and the mixture was degassed again. The reaction was heated to 80-90° C. and stirred overnight. The mixture was cooled. The organic layer was separated and concentrated. The residue was purified by prep. HPLC to afford (2S)-1-(4-(3-(6-amino-5-methylpyridin-3-yl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-3) (0.057 g, 11.6%) 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-91f4740973cd4913bbb4e0d6a017f881
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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