1-Butanol → 6-(3-Fluorophenyl)-N-(1-{9-[1-(hydroxymethyl)propyl]-9H-purin-6-yl}piperidin-4-yl)nicotinamide

HRID 602093노트

반응식

HRID 602093 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:22]=[CH:21][C:11]([C:12]([NH:14][CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[O:13])=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2[CH:33]([CH2:36][CH3:37])[CH2:34][OH:35].C(O)CCC.O>C(N(CC)CC)C>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:22]=[CH:21][C:11]([C:12]([NH:14][CH:15]3[CH2:16][CH2:17][N:18]([C:24]4[N:32]=[CH:31][N:30]=[C:29]5[C:25]=4[N:26]=[CH:27][N:28]5[CH:33]([CH2:34][OH:35])[CH2:36][CH3:37])[CH2:19][CH2:20]3)=[O:13])=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 2631-ButanolHCID 962WaterHCID 542456872-(6-chloro-9H-purin-9-yl)butan-1-olHCID 672679066-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide

생성물 1

HCID 249910426-(3-Fluorophenyl)-N-(1-{9-[1-(hydroxymethyl)propyl]-9H-purin-6-yl}piperidin-4-yl)nicotinamide

시약·촉매·용매 1

HCID 8471Triethylamine용매

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온도
85 °C

실험 절차

6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide (2.0 g, 5.37 mmol) and 2-(6-chloro-9H-purin-9-yl)butan-1-ol (1.58 g, 6.98 mmol) were placed in a flask along with 10 mL of butanol, 10 mL of water and 10 mL of triethylamine. The mixture was heated to 85° C. for 2 hours. The reaction mixture was partitioned between ethyl acetate and brine. The ethyl acetate was washed 3× with brine and then dried over MgSO4, filtered and concentrated. The residue was purified by chromatography (silica, 1.5% EtOH/EtOAc) to give the desired racemic product (Example 88, 1.34 g, 57%). The material was purified by chiral chromatography-SFC (50% iPrOH in CO2, AD-H 30×250 mm col) to give the two peaks (enantiomeric pair)

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate and brine
  2. washThe ethyl acetate was washed 3× with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (silica, 1.5% EtOH/EtOAc)
  7. customto give the desired racemic product (Example 88, 1.34 g, 57%)
  8. customThe material was purified by chiral chromatography-SFC (50% iPrOH in CO2, AD-H 30×250 mm col)
  9. customto give the two peaks (enantiomeric pair)

출처 및 근거

ORD 기록
ord-311ba459ea854e0987c1f730f871884b
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902373B2

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