Potassium Carbonate → HCID 89924531, compound

HRID 1505671Notes

Reaction equation

HRID 1505671 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=2)[NH2:11])=[N:6][CH:7]=1.B(O)(O)[C:16]1[CH:20]=[N:19][N:18]([CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.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>[NH2:11][C:10]1[CH:9]=[C:8]([C:5]2[N:4]=[CH:3][C:2]([C:16]3[CH:20]=[N:19][N:18]([CH:21]4[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]4)[CH:17]=3)=[CH:7][N:6]=2)[CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 46739790{1-[1-(tert-Butoxycarbonyl)piperidin-4-yl]-1H-pyrazol-4-yl}boronic acidHCID 63318778HCID 63318778, compound2×

Product 1

HCID 89924531HCID 89924531, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of 3-(5-bromopyrimidin-2-yl)aniline (intermediate 4, 220 mg; 0.88 mmol; 1.0 eq.), 1-(1-Boc-piperidino)pyrazole-4-boronic acid (389 mg; 1.3 mmol; 1.5 eq.), Pd(PPh3)4 (51 mg; 0.04 mmol; 0.05 eq.) and K2CO3 (365 mg; 2.6 mmol; 3.0 eq.) in dioxane/water (3.3: 1.65 mL) was heated at 12000 for 30 min in a sealed tube in MW. The reaction mixture was then diluted with EtOAc. The two phases were separated and aqueous phase was extracted with EtOAc. Combined organic phases were dried over magnesium sulfate, filtered and concentrated. Flash chromatography on silica (EtOAc:heptane, gradient from 50:50 to 100:0) afforded the title compound a beige solid (240 mg; 65%). 1H NMR (300 MHz, DMSO-d6) δ 9.09 (s, 2H), 8.52 (s, 1H), 8.11 (s, 1H), 7.67 (t, J=2.0 Hz, 1H), 7.57-7.53 (m, 1H), 7.14 (t, J=7.8 Hz, 1H), 6.69-6.66 (m, 1H), 5.25 (s, 2H), 4.46-4.36 (m, 1H), 4.08-4.04 (m, 2H), 2.94 (m, 2H), 2.08-2.04 (m, 2H), 1.87-1.75 (m, 2H), 1.43 (s, 9H). HPLC (Condition A): Rt 3.03 min (purity 99.0%). MS (ESI+): 421.4.

Workup

  1. temperaturewas heated at 12000 for 30 min in a sealed tube in MW
  2. customThe two phases were separated
  3. extractionaqueous phase was extracted with EtOAc
  4. dry with materialCombined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0f1447481c8f46baba40f93663df25e0
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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