1-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (Rac)-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

HRID 69229ノート

反応式

HRID 69229 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:22]=[CH:21][C:16]4[N:17]=[CH:18][N:19]([CH3:20])[C:15]=4[CH:14]=3)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][CH2:30][CH2:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1>COCCOC>[CH3:20][N:19]1[C:15]2[CH:14]=[C:13]([CH:11]([C:8]3[N:6]4[N:7]=[C:2]([C:35]5[CH:34]=[N:33][N:32]([CH2:31][CH2:30][O:29][CH:24]6[CH2:25][CH2:26][CH2:27][CH2:28][O:23]6)[CH:36]=5)[CH:3]=[CH:4][C:5]4=[N:10][CH:9]=3)[CH3:12])[CH:22]=[CH:21][C:16]=2[N:17]=[CH:18]1

参加物

4

反応物 2

HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87524205(Rac)-6-chloro-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine

生成物 1

HCID 68633396(Rac)-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

(rac)-6-Chloro-3-[1-(3-methyl-3H-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Stage 185.2, 525 mg, 1.381 mmol) was introduced in a microwave reactor together with 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3 ,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 667 mg, 2.071 mmol) and DME (9 mL). The mixture was purged with Argon for 5 min. Pd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added and the mixture was flushed with Argon before being sealed. It was then heated at 90° C. for 4,5 h. The RM was diluted with EtOAc and washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound as an oil (tR 2.39 min (conditions 8), MH+=472).

後処理

  1. customThe mixture was purged with Argon for 5 min
  2. additionPd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added
  3. customthe mixture was flushed with Argon
  4. custombefore being sealed
  5. additionThe RM was diluted with EtOAc
  6. washwashed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min)
  11. additionThe collected fractions containing product
  12. customwere evaporated
  13. customthe residue was dried under vacuum

出典と根拠

ORDレコード
ord-e894ed16d7404d4bb8d61c2d32eb7ede
出典データセット
uspto-grants-2014_09
特許番号
US08822468B2

反応ノート

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