Sodium Carbonate → HCID 89935960, compound

HRID 1505694Notes

Reaction equation

HRID 1505694 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[CH:9]=2)=[N:6][CH:7]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[CH:37]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:35]=[N:34]2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[CH3:19][N:17]1[CH:18]=[C:14]([C:10]2[CH:9]=[C:8]([C:5]3[N:4]=[CH:3][C:2]([C:36]4[CH:35]=[N:34][N:33]([CH:30]5[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]5)[CH:37]=4)=[CH:7][N:6]=3)[CH:13]=[CH:12][CH:11]=2)[CH:15]=[N:16]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 899239765-Bromo-2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]pyrimidine2×

Product 1

HCID 89935960HCID 89935960, compoundYield 94.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-bromo-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine (intermediate 2, 160 mg, 0.50 mmol), 4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Combi-blocks, 287 mg, 0.76 mmol) and Na2CO3 (140 mg, 0.12 mmol) in dry Toluene: Ethanol (1:1) (5 mL) was purged with nitrogen for 30 min before the addition of Pd(PPh3)4 (60 mg, 0.05 mmol). The reaction mixture was then heated at 100° C. O/N and filtered through a celite pad. The filtrate was concentrated under reduced pressure to give the crude product. Purification by Flash chromatography on silica (hexane:EtOAc) afforded the title compound as a yellow solid (230 mg, 93%). 1H NMR (400 MHz, DMSO-d6): δ 9.15 (s, 2H), 8.53 (d, J=8.0 Hz, 2H), 8.25 (s, 1H), 8.21 (d, J=7.76 Hz, 1H), 8.14 (s, 1H), 7.91 (s, 1H), 7.91-7.48 (m, 10H), 4.45-4.44 (m, 1H), 4.07-4.04 (m, 2H), 3.88 (s, 3H), 2.12 (s, 2H), 2.70 (d, J=3.44 Hz, 1H), 2.08-2.05 (m, 2H), 1.86-1.76 (m, 2H), 1.42 (s, 9H). HPLC (Condition A): Rt 4.68 min (purity 87%). MS (ESI+): 486.2.

Workup

  1. filtrationO/N and filtered through a celite pad
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customto give the crude product
  4. customPurification by Flash chromatography on silica (hexane:EtOAc)

Sources & evidence

ORD record
ord-ec0fd737583d474084c676a5db9822b8
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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