Ethanol → 4-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amine

HRID 539353ノート

反応式

HRID 539353 の反応式
[C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:20]1[CH:21]=[CH:22][C:23]2[O:34][C:33]3([CH2:39][CH2:38][CH:37]([O:40][CH3:41])[CH2:36][CH2:35]3)[C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]=2[CH:25]=1.CCO>COCCOC.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:41][O:40][CH:37]1[CH2:38][CH2:39][C:33]2([C:26]3([N:30]=[C:29]([NH2:31])[C:28]([CH3:32])=[N:27]3)[C:24]3[CH:25]=[C:20]([C:6]4[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=4)[CH:21]=[CH:22][C:23]=3[O:34]2)[CH2:35][CH2:36]1

参加物

8

反応物 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 574164825-(1-Propynyl)pyridine-3-boronic Acid (contains varying amounts of Anhydride)2 回HCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

生成物 1

HCID 679793924-Methoxy-5''-methyl-5'-[5-(prop-1-yn-1-yl)pyridin-3-yl]dispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amine収率 42%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

5-(Prop-1-ynyl)pyridin-3-ylboronic acid (Intermediate 15, 57.4 mg, 0.36 mmol), (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (9.79 mg, 0.01 mmol), cesium carbonate (233 mg, 0.71 mmol) and 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 90 mg, 0.24 mmol) were dissolved in a 6:3:1 mixture of DME:EtOH:water (2 mL) and heated at 150° C. in a microwave reactor for 15 min. The mixture was concentrated and the residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL). The layers were separated and the organic layer was dried over MgSO4 and concentrated. Purification of the crude product by preparative chromatography afforded 41 mg of the title compound (42% yield). 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.22 (m, 1 H), 1.46 (m, 3 H), 1.81 (m, 2 H), 1.98 (m, 2 H), 2.09 (s, 3 H), 2.21 (s, 3 H), 3.10 (m, 1 H), 3.22 (s, 3 H), 6.70 (s, 2 H), 6.95 (d, 1 H), 6.99 (d, 1 H), 7.56 (d, 1 H), 7.91 (t, 1 H), 8.47 (d, 1 H), 8.67 (d, 1 H); MS (APCI+) m/z 415 [M+H]+.

後処理

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between EtOAc (7 mL) and sat. aq. NaHCO3 (5 mL)
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude product by preparative chromatography

出典と根拠

ORDレコード
ord-eecb33f106ac43c6910a720013a126cb
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

反応ノート

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