Potassium Carbonate → HCID 68514117, compound

HRID 2241390Notes

Reaction equation

HRID 2241390 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[CH:13]=2)O1.[F:28][C:29]1[CH:30]=[C:31]([NH:55]C(C2C(=O)N(C3C=CC(F)=CC=3)N=CC=2)=O)[CH:32]=[CH:33][C:34]=1[O:35][C:36]1[CH:41]=[CH:40][N:39]=[C:38]2[N:42]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[N:43]=[C:44](I)[C:37]=12.C(=O)([O-])[O-].[K+].[K+]>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>[NH2:55][C:31]1[CH:32]=[CH:33][C:34]([O:35][C:36]2[CH:41]=[CH:40][N:39]=[C:38]3[N:42]([CH2:46][C:47]4[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=4)[N:43]=[C:44]([C:9]4[CH:10]=[N:11][N:12]([CH:14]5[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]5)[CH:13]=4)[C:37]=23)=[C:29]([F:28])[CH:30]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 68513145HCID 68513145, compound

Product 1

HCID 68514117HCID 68514117, compoundYield 36.1%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A 100 mL round-bottomed flask was charged with tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.289 g, 0.765 mmol), 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.250 g, 0.510 mmol from Example 63, Step A), potassium carbonate (0.106 g, 0.765 mmol), Pd(PPh3)4 (0.0295 g, 0.0255 mmol), degassed DMF (2 mL) and water (0.5 mL). The reaction mixture was heated at 100° C. using a CEM microwave for 2 hours. The reaction mixture was cooled to ambient temperature and extracted with EtOAc/water. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by preparative TLC (2.0 mm eluting with EtOAc). Isolated 0.113 g (32%) of the desired product. LRMS M+1 (614.1) observed.

Workup

  1. customdegassed DMF (2 mL) and water (0.5 mL)
  2. customfor 2 hours
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. extractionextracted with EtOAc/water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by preparative TLC (2.0 mm eluting with EtOAc)

Sources & evidence

ORD record
ord-c52bde28fad344658b80185e26c63a0f
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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