Sodium Carbonate → 3-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-amine

HRID 1959349ノート

反応式

HRID 1959349 の反応式
Br[C:2]1[N:3]=[C:4]([C:9]2[NH:13][C:12]3[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=3[N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[O:19]1[C:23]2([CH2:28][CH2:27][C:26](B(O)O)=[CH:25][CH2:24]2)[O:22][CH2:21][CH2:20]1.C(P(CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd]Cl.CCOC(C)=O>[CH3:18][C:15]1[CH:16]=[CH:17][C:11]2[N:10]=[C:9]([C:4]3[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:26]4[CH2:27][CH2:28][C:23]5([O:22][CH2:21][CH2:20][O:19]5)[CH2:24][CH:25]=4)[N:3]=3)[NH:13][C:12]=2[CH:14]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 27365TriethylphosphineHCID 441187651,4-Dioxaspiro[4.5]dec-7-en-8-ylboronic acidHCID 580842975-bromo-3-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-amine

生成物 1

HCID 461992483-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-amine収率 63%

試薬・触媒・溶媒 3

HCID 24290Palladium Chloride触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 5-bromo-3-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-amine (150 mg, 0.4932 mmol), 1,4-dioxaspiro[4.5]dec-7-en-8-ylboronic acid (181.5 mg, 0.9864 mmol), dichloropalladium; triethylphosphane (10.20 mg, 0.02466 mmol) and Na2CO3 (740.0 μL of 2 M, 1.480 mmol) were heated in DMF (1.500 mL) at 130° C. in a microwave for 30 min. EtOAc was added and the organic phase washed with saturated aqueous Na2CO3, dried (MgSO4) and concentrated in vacuo. The resulting oil was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (113 mg, 63% Yield). 1H NMR (400.0 MHz, DMSO) d 1.86 (t, J=6.4 Hz, 2H), 2.45 (m, 5H), 2.76 (s, 2H), 3.95 (s, 4H), 6.61 (t, J=3.9 Hz, 1H), 7.07 (dd, J=1.3, 8.3 Hz, 1H), 7.38 (s, 1H), 7.48 (d, J=8.2 Hz, 1H), 7.54 (s, 1H), 7.62 (d, J=8.3 Hz, 1H), 8.31 (d, J=4.0 Hz, 1H) and 8.37 (s, 1H) ppm; MS (ES+) 364

後処理

  1. washthe organic phase washed with saturated aqueous Na2CO3
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting oil was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  5. customThe fractions were collected
  6. customfreeze-dried

出典と根拠

ORDレコード
ord-aef46d874dc847bb8510c8eb93f8b16e
出典データセット
uspto-grants-2013_04
特許番号
US08410112B2

反応ノート

読み込み中…