Sodium Carbonate → (S,E)-Ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 1630324노트

반응식

HRID 1630324 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].[CH3:28][CH:29]([CH3:36])[CH2:30]/[CH:31]=[CH:32]/B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[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/[CH:32]=[CH:31]/[CH2:30][CH:29]([CH3:36])[CH3:28])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 60815074-Methyl-1-pentenylboronic acidHCID 86691589HCID 86691589, 화합물

생성물 1

HCID 71267861(S,E)-Ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °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 (300 mg, 0.613 mmol), (E)-(4-methylpent-1-en-1-yl)boronic acid (94 mg, 0.736 mmol) and 2N Na2CO3 (0.613 mL, 1.226 mmol) in DMF (6 mL) was degassed for 15 min. Tetrakis(triphenylphosphine)palladium(0) (49.6 mg, 0.043 mmol) was then added and the degassing was continued for another 5 min. The mixture was then heated at 100° C. for 2 h. At this point LCMS indicated completion of reaction and presence of desired product. After cooling to room temperature, water was added (10 mL) and the mixture was extracted with ether (2×50 mL), washed with brine (25 mL), dried (Na2SO4), filtered and concentrated. the crude was then purified by biotage (5-30% EtOAc/hexane) to afford (S,E)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate (200 mg, 0.449 mmol, 73.2% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.09 (s, 1H), 7.07 (s, 0.6H), 7.04 (s, 1H), 5.57 (s, 1H), 4.49 (q, J=7.1 Hz, 2H), 4.33-4.20 (m, 2H), 2.70 (s, 3H), 2.40 (td, J=7.0, 1.3 Hz, 2H), 1.90 (dt, J=13.4, 6.7 Hz, 1H), 1.46 (t, J=7.1 Hz, 3H), 1.29 (t, J=7.1 Hz, 3H), 1.17 (s, 9H), 1.06 (dd, J=6.6, 2.7 Hz, 6H). LCMS (M+H)=446.4.

후처리

  1. customwas degassed for 15 min

출처 및 근거

ORD 기록
ord-532f720e245d469a8d4ffc39d5078ac7
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791108B2

반응 노트

불러오는 중…