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

HRID 338252ノート

反応式

HRID 338252 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 2M 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., 1H), 10.02 (s, 1H), 8.59 (s, 1H), 8.21 (s, 1H), 8.13 (s, 1H), 7.64 (d, J=8.3 Hz, 2H), 7.56 (d, J=8.3 Hz, 2H), 5.59 (s, 1H), 2.48-2.43 (m, 2H), 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-bf1965fc12ce438d976f41bd353b7b36
出典データセット
uspto-grants-2014_11
特許番号
US08889730B2

反応ノート

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