Water → tert-butyl {1-[4-(9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

HRID 1046994ノート

反応式

HRID 1046994 の反応式
Br[C:2]1[N:6]2[C:7]3[CH:19]=[CH:18][CH:17]=[N:16][C:8]=3[NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[CH:32][C:31]([C:34]3([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:37][CH2:36][CH2:35]3)=[CH:30][CH:29]=2)O1.C([O-])(O)=O.[Na+].O>C1(C)C(CCO)=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][C:31]([C:34]3([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:43])([CH3:42])[CH3:44])[CH2:35][CH2:36][CH2:37]3)=[CH:32][CH:33]=2)[N:6]2[C:5]=1[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:8]1[N:16]=[CH:17][CH:18]=[CH:19][C:7]2=1

参加物

7

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamateHCID 675039063-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine

生成物 1

HCID 69087639tert-butyl {1-[4-(9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 882672-Methylphenethyl alcohol溶媒

実験手順

A mixture of 3-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine (1.48 g, 4.7 mmol), tert-butyl {1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate (2.12 g, 5.7 mmol), sat.NaHCO3 (4 mL), and tetrakis(triphenylphosphine)palladium(0) (0.55 g, 0.47 mmol) in toluene-ethanol (1/1, 40 mL) was heated to refluxed temperature for 15 hours. After cooling to room temperature the reaction mixture was poured into water and extracted with ethyl acetate. The organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (hexane/ethyl acetate) to give a yellow solid (quant.). 1HNMR (CDCl3) 400 MHz δ: 8.09-8.06 (m, 2H), 7.39 (s, 1H), 7.37(d, J=8.0 Hz, 2H), 7.30 (td, J=7.6, 1.5 Hz, 1H), 7.15 (d, J=8.0 Hz, 2H), 7.16-7.10 (m, 1H), 6.98 (dd, J=8.0, 1.2 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.70 (dd, J=7.7, 4.9 Hz, 1H), 6.27 (s, 1H), 5.08 (s, 1H), 2.57-2.39 (m, 4H), 2.18-2.07 (m, 1H), 1.93-1.84 (m, 1H), 1.48-1.19 (brs, 9H); LC/MS [M+H]: 480.

後処理

  1. temperatureto refluxed temperature for 15 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas evaporated in vacuo
  7. customThe crude product was purified by silica gel chromatography (hexane/ethyl acetate)
  8. customto give a yellow solid (quant.)

出典と根拠

ORDレコード
ord-70bfd116120745b78d8be207ce7afe87
出典データセット
uspto-grants-2013_10
特許番号
US08569331B2

反応ノート

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