Nitrogen → 2-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(3,6-dihydro-2H-pyran-4-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 57715ノート

反応式

HRID 57715 の反応式
[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23](I)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH2:34][CH2:35][O:36][CH2:37][CH:38]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N.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>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23]([C:33]4[CH2:38][CH2:37][O:36][CH2:35][CH:34]=4)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 1365928032-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-iodo-3H-imidazo[5,1-f][1,2,4]triazin-4-one

生成物 1

HCID 1362676462-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(3,6-dihydro-2H-pyran-4-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one収率 55.5%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

To a mixture of compound 6 (100 mg, 0.23 mmol) and 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (145 mg, 0.69 mmol) in DMF (10 mL) was added potassium phosphate (146 mg, dissolved in 1 mL of H2O). The reaction mixture was degassed by purging with N2 for 15 min, before Pd(dppf)2Cl2 (28 mg, 0.035 mmol) and Xantphos (40 mg, 0.069 mmol) were added. The resulting suspension was bubbled with nitrogen for 10 minutes. The reaction mixture was heated to 150° C. under microwave irradiation for one hour. After cooling down, the reaction mixture was diluted with EtOAc (50 mL), and the precipitate was filtered off. The filtrate was washed with brine (50 mL), dried over Na2SO4, filtered and the filtrate was concentrated. The crude product was purified by column chromatography on silica gel (eluting with EtOAc) to afford 7 (50 mg, 55% yield) as a white solid. LC-MS: m/z 393.03 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 7.85 (s, 1H), 7.37˜7.22 (m, 6H), 4.40 (d, J=2.8 Hz, 2H), 3.95˜3.92 (m, 2H), 3.82˜3.79 (d, J=12.6 Hz, 1H), 3.61˜3.58 (d, J=12.6 Hz, 1H), 3.39˜3.37 (m, 1H), 3.00˜2.98 (d, J=10.0 Hz, 1H), 2.76˜2.73 (m, 3H), 2.54˜2.52 (m, 1H), 2.44˜2.42 (m, 1H), 1.95˜1.90 (m, 2H), 1.21 (d, J=7.2 Hz, 3H).

後処理

  1. customThe reaction mixture was degassed
  2. additionwere added
  3. customThe resulting suspension was bubbled with nitrogen for 10 minutes
  4. temperatureAfter cooling down
  5. additionthe reaction mixture was diluted with EtOAc (50 mL)
  6. filtrationthe precipitate was filtered off
  7. washThe filtrate was washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customThe crude product was purified by column chromatography on silica gel (eluting with EtOAc)

出典と根拠

ORDレコード
ord-f5ce29b3f0b445798c98ca6fcf5252de
出典データセット
uspto-grants-2016_09
特許番号
US09434733B2

反応ノート

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