Sodium Carbonate → (2S)-1-(4-(3-(2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500725Notes

Reaction equation

HRID 500725 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[NH:39][C:25]2=[N:26][CH:27]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:29]=[C:24]2[C:23]=1[CH3:40].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>[CH3:21][C:22]1[NH:39][C:25]2=[N:26][CH:27]=[C:28]([C:2]3[C:6]([C:7]4[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=4)=[CH:5][N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=3)[CH:29]=[C:24]2[C:23]=1[CH3:40]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 533986342,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

Product 1

HCID 25183620(2S)-1-(4-(3-(2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-olYield 23.6%

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) (0.34 g, 0.885 mmol) in toluene (30 mL) and EtOH (10 mL) were added 2,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (B-6-5) (0.7 g, 1.77 mmol in theory) and 2 N aq. Na2CO3 (1.3 mL). The resulting mixture was degassed under N2 for 2 minutes. Then Pd(PPh3)4 (68 mg, 0.058 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-(2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-6) (0.170 mg, 23.6%) 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-e076daee04984cdb95ce06bf8da583a1
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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