Diisopropylethylamine → ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 921163ノート

反応式

HRID 921163 の反応式
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1I)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[Si:28]([O:45][C@H:46]([CH3:59])[CH2:47][CH2:48][CH2:49][CH2:50][O:51][C:52]1([CH3:58])[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)([C:41]([CH3:44])([CH3:43])[CH3:42])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOCC>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1[N:55]1[CH2:56][CH2:57][C:52]([O:51][CH2:50][CH2:49][CH2:48][CH2:47][C@H:46]([O:45][Si:28]([C:41]([CH3:42])([CH3:44])[CH3:43])([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH3:59])([CH3:58])[CH2:53][CH2:54]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 86691589HCID 86691589、化合物HCID 123395765(R)-4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine

生成物 1

HCID 131734908ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate収率 80.1%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
70 °C

実験手順

A mixture of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (5.25 g, 10.73 mmol) in NMP (80 mL) was treated with (R)-4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine (6.33 g, 13.95 mmol) and Hunig's Base (5.62 mL, 32.2 mmol), and the mixture was heated (70° C. oil bath) for 16 hrs. At this point LCMS indicates completion of reaction. Mixture was then cooled, diluted with Et2O (200 mL) and washed with water (100 mL) and brine (50 mL), then dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then purified by Biotage (5-15%) EtOAc Hexane to afford ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (7, 8.59 mmol, 80% yield) as viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J=8.0, 1.5 Hz, 4H), 7.47-7.28 (m, 6H), 7.01 (s, 1H), 5.82 (br. s., 1H), 4.50-4.38 (m, 2H), 4.31-4.07 (m, 2H), 3.94-3.77 (m, 1H), 3.41-3.24 (m, 3H), 2.61 (s, 3H), 1.88 (br. s., 2H), 1.67 (br. s., 1H), 1.54 (br. s., 1H), 1.51-1.39 (m, 5H), 1.30 (s, 3H), 1.26-1.23 (m, 6H), 1.22 (s, 9H), 1.08 (s, 3H), 1.06 (s, 9H). 4 missing piperidine hydrogens. LCMS (M+H)=816.4.

後処理

  1. customcompletion of reaction
  2. temperatureMixture was then cooled
  3. washwashed with water (100 mL) and brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by Biotage (5-15%) EtOAc Hexane

出典と根拠

ORDレコード
ord-e3c5ae6750544883ac0da7c811475e6e
出典データセット
uspto-grants-2016_03
特許番号
US09273067B2

反応ノート

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