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Aniline → 12-N-[4-(dimethylamino)cyclohexyl]-10-N-phenyl-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene-10,12-diamine

HRID 2369424
ノート
印刷プレビュー

反応式

HRID 2369424 の反応式
Cl[C:2]1[N:13]=[C:12]([NH:14][CH:15]2[CH2:20][CH2:19][CH:18]([N:21]([CH3:23])[CH3:22])[CH2:17][CH2:16]2)[C:11]2[C:10]3[CH2:9][CH2:8][CH2:7][C:6]=3[S:5][C:4]=2[N:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:22][N:21]([CH3:23])[CH:18]1[CH2:19][CH2:20][CH:15]([NH:14][C:12]2[C:11]3[C:10]4[CH2:9][CH2:8][CH2:7][C:6]=4[S:5][C:4]=3[N:3]=[C:2]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:13]=2)[CH2:16][CH2:17]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 6115AnilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866733354-N-[10-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine

生成物 1

HCID 5751999412-N-[4-(dimethylamino)cyclohexyl]-10-N-phenyl-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene-10,12-diamine収率 14.4%

試薬・触媒・溶媒

2
HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

A solution of 4-N-[10-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (120 mg, 0.34 mmol, 1.00 equiv) in dioxane (5 mL), was added aniline (60 mg, 0.72 mmol, 2.00 equiv), XantPhos (20 mg, 0.03 mmol, 0.10 equiv) and Pd2(dba)3 (20 mg, 0.02 mmol, 0.06 equiv) subsequently under nitrogen. The resulting solution was stirred overnight at 110° C. After completion of the reaction, the solids were filtered out and the filtrate was diluted with DCM, washed with brine. The organic layer was concentrated under vacuum and the crude product (80 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (25% CH3CN up to 100% in 15 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the 12-N-[4-(dimethylamino)cyclohexyl]-10-N-phenyl-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene-10,12-diamine (20 mg) as a grey solid. LCMS (ES, m/z): 408 [M+H]+;

後処理

  1. customAfter completion of the reaction
  2. filtrationthe solids were filtered out
  3. additionthe filtrate was diluted with DCM
  4. washwashed with brine
  5. concentrationThe organic layer was concentrated under vacuum
  6. customthe crude product (80 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  7. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (25% CH3CN up to 100% in 15 min)
  8. customThe product-containing fractions were collected
  9. custompartially evaporated
  10. customto remove water and CH3CN under reduced pressure
  11. waitThe residue was lyophilized overnight

出典と根拠

ORDレコード
ord-acf71171070548c7b824a259c50dc8cb
出典データセット
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08703941B2

反応ノート

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