Sodium Bicarbonate → 8-(4-Benzyloxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one

HRID 925548노트

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HRID 925548 반응식
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22]3[C:21](=[O:32])[N:20]([CH2:33][CH2:34][CH3:35])[C:19](Cl)=[N:18][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:37][C:38]([F:49])([F:48])[C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=1.C([O-])(O)=O.[Na+]>C1COCC1.O.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>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22]3[C:21](=[O:32])[N:20]([CH2:33][CH2:34][CH3:35])[C:19]([C:43]4[CH:42]=[CH:41][CH:40]=[C:39]([C:38]([F:49])([F:48])[F:37])[CH:44]=4)=[N:18][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 674976248-(4-Benzyloxy-phenyl)-2-chloro-1-propyl-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one

생성물 1

HCID 674975388-(4-Benzyloxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one수율 11.2%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 178418397HCID 178418397, 화합물용매

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온도
85 °C

실험 절차

A mixture of 8-(4-benzyloxy-phenyl)-2-chloro-1-propyl-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one (50.0 mg, 0.96 mmol), 3-Trifluoromethyl phenyl boronic acid (31.0 mg, 1.4 mmol) were taken in THF (5 ml) and degassed for 10 minutes. To above degassed solution NaHCO3 (20.0 mg, 0.24 mmol) in water (1 ml) and Pd(PPh3)4 were added and degassed for another 20 minutes. The reaction mixture was stirred for 28 hours at 80-90° C. The mixture was cooled to 25-27° C. and diluted with water (5 ml). The aqueous layer was extracted with DCM (3×5 ml). The organic layer was washed with brine (2×10 ml), dried over Na2SO4, and the solvent was evaporated. The residue obtained was purified by preparative TLC (35% Ethyl acetate in hexane) to obtain pure 8-(4-Benzyloxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one (68 mg, quantitative) as a yellow solid.

후처리

  1. customdegassed for 10 minutes
  2. additionwere added
  3. customdegassed for another 20 minutes
  4. temperatureThe mixture was cooled to 25-27° C.
  5. additiondiluted with water (5 ml)
  6. extractionThe aqueous layer was extracted with DCM (3×5 ml)
  7. washThe organic layer was washed with brine (2×10 ml)
  8. dry with materialdried over Na2SO4
  9. customthe solvent was evaporated
  10. customThe residue obtained
  11. customwas purified by preparative TLC (35% Ethyl acetate in hexane)

출처 및 근거

ORD 기록
ord-ca56912052d2413f8b6dddc5e4163e89
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284316B2

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