Potassium Carbonate → 3-formyl-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-6-carbonitrile

HRID 1054595ノート

反応式

HRID 1054595 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[C:11]#[N:12])[NH:7][CH:6]=[C:5]2[CH:13]=[O:14].CC1(C)COB([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([OH:32])[CH2:31][CH2:30][CH2:29]3)=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C(O)C.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]>[CH:13]([C:5]1[C:4]2[C:8](=[CH:9][C:10]([C:11]#[N:12])=[C:2]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4([OH:32])[CH2:31][CH2:30][CH2:29]4)=[CH:24][CH:23]=3)[CH:3]=2)[NH:7][CH:6]=1)=[O:14]

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 866985671-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)cyclobutanol2 回HCID 866985965-bromo-3-formyl-1H-indole-6-carbonitrile

生成物 1

HCID 866985983-formyl-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-6-carbonitrile収率 70.5%

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

A suspension of 5-bromo-3-formyl-1H-indole-6-carbonitrile (250 mg, 1.00 mmol), 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclobutanol (300 mg, 1.16 mmol) and 2 M aqueous potassium carbonate solution (1.26 mL, 2.51 mmol) in toluene (2.1 mL) and ethanol (1.25 mL) was degassed with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (73.2 mg, 0.1 mmol) and heated to 85° C. for 1 hour, at which point the reaction mixture was treated with a solution of 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclobutanol (40 mg) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30 mg) in DMF (0.6 mL). After 3.5 hours, the clear red reaction mixture was cooled to room temperature and poured into half-diluted ammonium chloride solution (100 mL). The product was extracted with ethyl acetate (6×70 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The crude product was purified using flash chromatograph eluting with heptanes/ethyl acetate (with 0.2% formic acid) (9:1 to 1:9) to give the title compound (223 mg, 70%) as an off-white solid. MS (ES−) 315.2 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ 12.62 (br. s., 1 H), 10.02 (s, 1 H), 8.59 (s, 1 H), 8.21 (s, 1 H), 8.13 (s, 1 H), 7.64 (d, J=8.3 Hz, 2 H), 7.56 (d, J=8.3 Hz, 2 H), 5.59 (s, 1 H), 2.48-2.43 (m, 2 H), 2.32-2.25 (m, 2H), 2.01-1.92 (m, 1H), 1.77-1.67 (m, 1H).

後処理

  1. customwas degassed with nitrogen for 10 minutes
  2. customthe clear red reaction mixture
  3. temperaturewas cooled to room temperature
  4. extractionThe product was extracted with ethyl acetate (6×70 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified
  9. washeluting with heptanes/ethyl acetate (with 0.2% formic acid) (9:1 to 1:9)

出典と根拠

ORDレコード
ord-5bd3f4280ca8419ca9a7d3b6dbd37981
出典データセット
uspto-grants-2016_07
特許番号
US09394285B2

反応ノート

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