8-Amino-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one → 1,4-Diethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-8-ylamine

HRID 1687336ノート

反応式

HRID 1687336 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=O)[N:10]([CH2:13][CH3:14])[CH2:9][CH2:8][N:7]([CH2:15][CH3:16])[C:6]=2[CH:17]=1>O1CCOCC1.C1COCC1>[CH2:15]([N:7]1[C:6]2[CH:17]=[C:2]([NH2:1])[CH:3]=[CH:4][C:5]=2[CH2:11][N:10]([CH2:13][CH3:14])[CH2:9][CH2:8]1)[CH3:16]

参加物

4

反応物 1

HCID 672633818-Amino-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one

生成物 1

HCID 672642811,4-Diethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-8-ylamine収率 84%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

To a solution of 8-Amino-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5one (22.0 g, 0.0944 mol) in dioxane (400 mL) was added borane dimethyl sulfide complex solution (2 M in THF, 118 mL, 0.236 mol) and heated at 75° C. for 4 hr. The reaction was quenched with ethanol (100 mL) and stirred at room temperature for 18 hr., then evaporated. To the residue was added hydrazine hydrate (100 mL) and heated at 95° C. for 4 hr. After evaporation, toluene (50 mL) and ethanol (50 mL) were added, distilled and the reaction evaporated. The residue was extracted with DCM, evaporated, dissolved in ether, filtered and evaporated to give 1,4-Diethyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamine as an oil (16.0 g, 84%). LCMS (m/e) 220 (M+1); 1H-NMR (DMSO, 400 MHz) δ 6.79-6.71 (d, 1H, J=7.83 Hz), 6.49 (br, 1H), 6.01-5.99 (d, 1H, J=7.83 Hz), 4.79 (s, 2H), 3.07-3.02 (q, 2H, J=6.82 Hz), 2.85-2.83 (t, 2H, J=8.08 Hz), 2.70-2.68 (t, 2H, J=8.09 Hz), 1.13-1.10 (t, 3H, J=7.07 Hz), 1.00-0.97 (t, 3H, J=7.32 Hz), 712d) 5-Chloro-N*2*-(1,4-diethyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-yl)-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidin-2,4-diamine was prepared from 1,4-Diethyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamine (0.068 g, 0.00023 mol) and (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (0.081 g, 0.00023 mol), camphorsulfonic acid (0.0187 g, 0.0008 mol) and methoxyethanol (10 mL). The mixture was heated at 95° C. for 18 hr. The reaction was evaporated and the residue treated with a 10% sodium carbonate solution and DCM, separated, washed, dried and evaporated to give a solid. This material was chromatographed on a silica gel prep plate with THF/methanol (10-1) giving the product as a tan solid (0.053 g, 43%). Mp 165-166° C. LCMS (m/e) 538 (M); 1H-NMR (DMSO, 400 MHz) δ 9.07 (s, 1H), 8.05 (s, 1H), 8.01 (s, 1H), 7.65 (d, 1H), 7.15-7.13 (d, 1H, J=8.33 Hz), 7.01 (s, 1H), 6.84-6.82 (d, 1H, J=8.08 Hz), 6.69 (s, 1H), 6.49-6.47 (d, 1H, J=8.59 Hz), 3.80 (s, 3H), 3.76 (t, 2H, J=4.05), 3.54 (s, 2H), 3.14 (t, 3H), 3.01-2.99 (q, 2H, J=7.07 Hz), 2.90-2.84 (m, 2H), 2.78-2.69 (m, 2H), 2.40-2.30 (m, 2H), 1.11-1.08 (t, 3H, J=6.57 Hz), 1.03-1.00 (t, 3H, J=7.33).

後処理

  1. customThe reaction was quenched with ethanol (100 mL)
  2. custom, then evaporated
  3. additionTo the residue was added hydrazine hydrate (100 mL)
  4. temperatureheated at 95° C. for 4 hr
  5. customAfter evaporation, toluene (50 mL) and ethanol (50 mL)
  6. additionwere added
  7. distillationdistilled
  8. customthe reaction evaporated
  9. extractionThe residue was extracted with DCM
  10. customevaporated
  11. dissolutiondissolved in ether
  12. filtrationfiltered
  13. customevaporated

出典と根拠

ORDレコード
ord-22e4d583d24f4f88838040a4465b5f94
出典データセット
uspto-grants-2012_04
特許番号
US08148391B2

反応ノート

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