1,2-Dimethoxyethane → 3-{4-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester

HRID 69185Notes

Reaction equation

HRID 69185 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.[C:23]([O:27][C:28]([N:30]1[CH2:33][CH:32]([N:34]2[CH:38]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:36]=[N:35]2)[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].COCCOC.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.C([O-])(O)=O.[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:23]([O:27][C:28]([N:30]1[CH2:33][CH:32]([N:34]2[CH:38]=[C:37]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]([C:8]([CH2:11][C:12]5[CH:13]=[C:14]6[C:19](=[CH:20][C:21]=5[F:22])[N:18]=[CH:17][CH:16]=[CH:15]6)=[CH:9][N:10]=4)[N:7]=3)[CH:36]=[N:35]2)[CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 54576812tert-Butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylateHCID 581475166-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline

Product 1

HCID 686331183-{4-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86584982Sodium bicarbonate ethyl acetateSolvent

Conditions

Temperature
95 °C

Procedure

A flask was charged with 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline (Stage 173.1, 100 mg, 0.320 mmol), 3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrazol-1-yl]-azetidine-1-carboxylic acid tert-butyl ester (Stage 146.3), 168 mg, 0.480 mmol), DME (2 mL), Pd(PPh3)2Cl2 (11 mg, 0.05 mmol) and 2 M K2CO3 (432 μL, 0.863 mmol). The RM was heated at 95° C. for 2 h. The cool RM was diluted with EtOAc/NaHCO3. The organic phase was separated and washed with brine (2×) then dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (CombiFlash® Companion System®, with a 4 g RediSep®: silica gel column, DCM/(DCM/MeOH 19:1)=100:0→0:100) to afford the title compound as a foam (tR 4.33 min (conditions 3), MH+=500.1).

Workup

  1. customThe organic phase was separated
  2. washwashed with brine (2×)
  3. dry with materialthen dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (CombiFlash® Companion System®

Sources & evidence

ORD record
ord-1324ea0a58dc41c08238689e578002a6
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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