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 921163노트

반응식

HRID 921163 반응식
[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]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 86691589HCID 86691589, 화합물HCID 123395765(R)-4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine

생성물 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-carboxylate수율 80.1%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e3c5ae6750544883ac0da7c811475e6e
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273067B2

반응 노트

불러오는 중…