1,8-Diazabicyclo(5.4.0)undec-7-ene → N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamine

HRID 2237405

反応式

HRID 2237405 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([NH2:13])[CH:10]=[C:9]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:8]=2)[CH2:3][CH2:2]1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[C:36]3[O:35][CH2:34][O:33][C:32]=3[CH:31]=[CH:30][C:29]=2[Cl:37])[CH:24]=[CH:23][N:22]=1.N12CCCN=C1CCCCC2.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>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.[Pd]>[Cl:37][C:29]1[CH:30]=[CH:31][C:32]2[O:33][CH2:34][O:35][C:36]=2[C:28]=1[NH:27][C:25]1[CH:24]=[CH:23][N:22]=[C:21]([NH:13][C:11]2[CH:10]=[C:9]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:8]=[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)[N:26]=1

参加物

7

反応物 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 426316842-chloro-N-(5-chloro-1,3-benzodioxol-4-yl)pyrimidin-4-amineHCID 575713742,6-Dimorpholin-4-ylpyridin-4-amine

生成物 1

HCID 42644813N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamine収率 29.6%

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

2,6-Dimorpholinopyridin-4-amine (140 mg, 0.53 mmol), 2-chloro-N-(5-chlorobenzo[d][1,3]dioxol-4-yl)pyrimidin-4-amine (150 mg, 0.53 mmol), 1,8-diazabicyclo-[5.4.0]-undec-7-ene (0.158 mL, 1.06 mmol), bis(dibenzylideneacetone)palladium(0) (45.5 mg, 0.08 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (92 mg, 0.16 mmol) were dissolved in dioxane (3 mL) and sealed into a microwave tube. The reaction was degassed, purged with nitrogen and heated at 120° C. overnight. The reaction mixture was filtered off and washed thoroughly with dichloromethane. The filtrate was concentrated to dryness, diluted with dichloromethane (15 ml), washed with water (30 ml) and brine (15 ml), dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamine (80 mg, 29.6%) as a pale beige foam. NMR Spectrum: (DMSOd6) 3.09-3.25 (m, 8H), 3.57-3.70 (m, 8H), 6.00 (s, 2H), 6.17 (d, 1H), 6.52 (s, 2H), 6.91 (d, 1H), 7.04 (d, 1H), 8.02 (d, 1H), 9.02 (s, 1H), 9.03 (s, 1H); Mass spectrum: MH+ 512.

後処理

  1. customsealed into a microwave tube
  2. customThe reaction was degassed
  3. custompurged with nitrogen
  4. filtrationThe reaction mixture was filtered off
  5. washwashed thoroughly with dichloromethane
  6. concentrationThe filtrate was concentrated to dryness
  7. additiondiluted with dichloromethane (15 ml)
  8. washwashed with water (30 ml) and brine (15 ml)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane
  12. customThe solvent was evaporated to dryness

出典と根拠

ORDレコード
ord-234bfa398b174387ba8d819a79ae1e8b
出典データセット
uspto-grants-2010_05
特許番号
US07718653B2

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