Sodium Carbonate → 1,1-dimethylethyl 5-(4-amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

HRID 1909933Notes

Reaction equation

HRID 1909933 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH3:12])[N:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25][CH2:24]3)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH3:12])[N:3]=[C:2]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25][CH2:24]4)[C:10]=12

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 127789343-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 18451469tert-butyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate

Product 1

HCID 668237181,1-dimethylethyl 5-(4-amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,3-dihydro-1H-indole-1-carboxylateYield 70.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a 25 mL pressure tube was charged 3-bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (670 mg, 2.94 mmol), 1,1-dimethylethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (1014 mg, 2.94 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (120 mg, 0.147 mmol), and sodium carbonate (494 mg, 5.88 mmol) followed by dioxane (8 mL), and water (2 mL). The reaction was heated at 120° C. for 40 minutes in a microwave reactor. LCMS showed no more SM. The reaction was cooled to room temperature, the mixture was transferred into a 100 mL Erlenmeyer flask, rinsed by EtOAc, with the water layer and black greasy solid stayed in tube (total 50 mL of EtOAc was added to the mixture). White solid was formed in brown solution. The solid was filtered to give titled product (764 mg).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washrinsed by EtOAc, with the water layer and black greasy solid
  3. customstayed in tube
  4. addition(total 50 mL of EtOAc was added to the mixture)
  5. customWhite solid was formed in brown solution
  6. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-3357db5901bb498fb3391804defe49e4
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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