Cesium carbonate → HCID 86679608、化合物

HRID 577662ノート

反応式

HRID 577662 の反応式
Cl[C:2]1[N:3]=[C:4]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:5]2[C:10]([F:11])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.C([O-])([O-])=O.[Cs+].[Cs+].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]>[F:11][C:10]1[C:5]2[C:4]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=3)=[N:3][C:2]([NH:36][C:33]3[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=3)=[N:7][C:6]=2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 1372541-Methyl-3-aminopyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86679606HCID 86679606、化合物

生成物 1

HCID 86679608HCID 86679608、化合物収率 95.2%

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
140 °C

実験手順

To a solution of 2-chloro-5-fluoro-4-(3-nitrophenoxy)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (483 mg, 1.1 mmol), in 1,4-dioxane (12 mL) was added 1-methyl-1H-pyrazol-3-amine (128 mg, 1.32 mmol), Cs2CO3 (717 mg, 2.2 mmol), Xantphos (66 mg, 0.11 mmol) and Pd2(dba)3 (101 mg, 0.11 mmol). The reaction vial was flushed with nitrogen, capped, stirred and heated at 140° C. in a microwave reactor for 45 min. After removing the reaction solvent, the residue was partitioned in EtOAc (120 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL) and brine (10 mL), dried over Na2SO4 and evaporated. Purification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes afforded the title compound (523 mg, 95% yield) as a thick oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.62 (s, 1H) 8.28-8.32 (m, 1H) 8.26 (d, J=8.06 Hz, 1H) 7.90-7.95 (m, 1H) 7.81-7.88 (m, 1H) 7.45 (br. s., 1H) 7.32 (d, J=2.27 Hz, 1H) 5.52 (s, 2H) 3.74 (s, 3H) 3.55-3.66 (m, 2H) 0.94 (t, J=8.18 Hz, 2H) 0.00 (s, 9H). m/z (APCI+) for C22H26FN7O4Si 500.1 (M+H)+.

後処理

  1. customThe reaction
  2. customvial was flushed with nitrogen
  3. customcapped
  4. customAfter removing the reaction solvent
  5. customthe residue was partitioned in EtOAc (120 mL)
  6. customThe organic layer was separated
  7. washwashed with water (20 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customPurification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes

出典と根拠

ORDレコード
ord-ebb5e206a3084a4c93c3c59aaaa088b3
出典データセット
uspto-grants-2015_05
特許番号
US09040547B2

反応ノート

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