1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

HRID 69278Notes

Reaction equation

HRID 69278 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]([CH3:23])[N:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1>COCCOC>[F:22][C:21]1[CH:20]=[C:19]2[C:15]([CH:16]=[N:17][N:18]2[CH3:23])=[CH:14][C:13]=1[CH:11]([C:8]1[N:6]2[N:7]=[C:2]([C:28]3[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1)[CH3:12]

Participants

4

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 581475176-Chloro-3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine

Product 1

HCID 57917432(Rac)-3-[1-(6-fluoro-1-methyl-1h-indazol-5-yl)-ethyl]-6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Stage 278.1), 240 mg, 0.728 mmol) was introduced in a microwave reactor together with 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (227 mg, 1.092 mmol) and DME (5 mL). The mixture was purged with argon for 5 min. Tetrakis-(triphenylphosphine)-palladium (42.1 mg) and 2 M Na2CO3 (1.31 mL) were added and the mixture was flushed with argon before being sealed. The RM was submitted to microwave irradiation at 150° C. 30 min. Then it was diluted with EtOAc and washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to afford the title compound as a white solid (tR 1.03 min (conditions 2), MH+=376) 1H-NMR in DMSO-d6: 8.29 (s, 1H); 8.05 (d, 1H); 7.93 (s, 1H); 7.67 (s, 1H); 7.58 (d, 1H); 7.53 (d, 1H); 7.46 (d, 1H); 7.23 (d, 1H); 4.92 (q, 1H); 3.94 (s, 3H); 3.88 (s, 3H); 1.76 (d, 3H)).

Workup

  1. customThe mixture was purged with argon for 5 min
  2. additionTetrakis-(triphenylphosphine)-palladium (42.1 mg) and 2 M Na2CO3 (1.31 mL) were added
  3. customthe mixture was flushed with argon
  4. custombefore being sealed
  5. customirradiation at 150° C
  6. custom30 min
  7. additionThen it was diluted with EtOAc
  8. washwashed with water, brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

Sources & evidence

ORD record
ord-24ce88310f264044800dd64c5aabcc93
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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