Potassium Carbonate → HCID 178453013, compound

HRID 869213Notes

Reaction equation

HRID 869213 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:12]=[N:11][C:10]([N:13]([CH2:21][C:22]3([C:26]4[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=4)[CH2:25][CH2:24][CH2:23]3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][CH:8]=2)=[N:4][CH:3]=1.[NH:33]1[C:37](B(O)O)=[CH:36][CH:35]=[N:34]1.O1CCOCC1.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C>[NH:33]1[CH:37]=[CH:36][C:35]([C:2]2[S:6][C:5]([C:7]3[N:12]=[N:11][C:10]([N:13]([CH2:21][C:22]4([C:26]5[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=5)[CH2:25][CH2:24][CH2:23]4)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[CH:9][CH:8]=3)=[N:4][CH:3]=2)=[N:34]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 112519791H-Pyrazole-5-boronic acidHCID 68232471HCID 68232471, compound

Product 1

HCID 178453013HCID 178453013, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial was added t-butyl 6-(5-bromothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (100 mg, 0.19 mmol), 1H-pyrazol-5-ylboronic acid (32 mg, 0.29 mmol), (dppf)PdCl2 (16 mg, 0.02 mmol), dioxane (2 mL), and K2CO3 (0.2 mL of a 2M aqueous solution, 38 mmol). The mixture was heated to 140° C. in a microwave reactor and stirred for 20 min. The reaction mixture was then poured into ethyl acetate (50 mL), washed with water (20 mL), dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (EtOAc/hex) to afford 38 mg of t-butyl 6-(5-(1H-pyrazol-3-yl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate. This compound was dissolved in CH2Cl2 (5 mL) and TFA (1 mL). The reaction was stirred for 30 min at rt, concentrated, and then purified using reverse phase chromatography to give 15 mg of 6-(5-(1H-pyrazol-3-yl)thiazol-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine, (M+H=408.3).

Workup

  1. washwashed with water (20 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (EtOAc/hex)

Sources & evidence

ORD record
ord-d8ca544af1324c84bd8304e885446649
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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