Hydrochloric Acid → 9-Cyclopentyl-N-(5-(3,5-dimethyl-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido-[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79178ノート

反応式

HRID 79178 の反応式
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH2:15])[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[C:19]([F:20])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:33][CH:32]([CH3:34])[NH:31][CH:30]([CH3:35])[CH2:29]2)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Cl>CO.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].C(OCC)C.O1CCOCC1>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:33][CH:32]([CH3:34])[NH:31][CH:30]([CH3:35])[CH2:29]5)=[CH:26][N:27]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[C:19]([F:20])[C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582995991-(6-Chloropyridin-3-yl)-3,5-dimethylpiperazineHCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

生成物 1

HCID 582998469-Cyclopentyl-N-(5-(3,5-dimethyl-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido-[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine収率 67%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A 10 mL reaction vessel was charged with compound 245 (80.0 mg, 295 μmol), 1-(6-chloropyridin-3-yl)-3,5-dimethylpiperazine (66.6 mg, 295 μmol), tris(dibenzylideneacetone)dipalladium (0) (20.3 mg, 22.1 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (25.6 mg, 44.2 μmol), sodium t-butoxide (56.7 mg, 590 μmol), and dioxane (2.5 mL). The reaction was purged with argon and heated with microwave energy (300 W) for 3.5 hours at 120° C. The reaction was taken up in ethyl acetate (40 mL) and washed with water (30 mL) and brine (30 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes+2.5% TEA/0-100% ethyl acetate+2.5% TEA, then ethyl acetate+2.5% TEA, 0-8% methanol) afforded a yellow solid. This residue was taken up in 2 mL methanol (2 mL) and 1M ethanolic HCl (1 mL) was added, followed by the addition of diethyl ether (20 mL). The resulting precipitate was collected and dried in vacuo to give compound 289 as a yellow solid (91 mg, 67%) 1H NMR (500 MHz, DMSO-d6) δ 9.54-9.67 (m, 2 H) 9.47-9.54 (m, 1 H) 9.05-9.23 (m, 1 H) 8.19-8.30 (m, 1 H) 8.06-8.17 (m, 3 H) 7.94-8.04 (m, 1 H) 7.81-7.94 (m, 1 H) 5.45-5.58 (m, 1 H) 3.81-3.94 (m, 2 H) 3.34-3.48 (m, 2 H) 2.75-2.91 (m, 2 H) 2.23-2.35 (m, 2 H) 2.10-2.20 (m, 2 H) 2.05 (none, 2 H) 1.68-1.86 (m, 2 H) 1.34 (d, J=6.60 Hz, 7 H) ppm.

後処理

  1. customA 10 mL reaction vessel
  2. customThe reaction was purged with argon
  3. washwashed with water (30 mL) and brine (30 mL)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. customevaporated
  6. customto give an orange oil
  7. washSilica gel chromatography (gradient elution hexanes+2.5% TEA/0-100% ethyl acetate+2.5% TEA
  8. customethyl acetate+2.5% TEA, 0-8% methanol) afforded a yellow solid
  9. customThe resulting precipitate was collected
  10. customdried in vacuo

出典と根拠

ORDレコード
ord-658a65ce8b6a43c395e3150bd08bbf03
出典データセット
uspto-grants-2014_09
特許番号
US08841312B2

反応ノート

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