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 539353노트

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HRID 539353 반응식
[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

참가 물질

8

반응물 4

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

생성물 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''-amine수율 42%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-eecb33f106ac43c6910a720013a126cb
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865911B2

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