Sodium Carbonate → Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 1630317노트

반응식

HRID 1630317 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].[Cl:28][C:29]1[C:38]2[NH:37][CH2:36][CH2:35][O:34][C:33]=2[CH:32]=[CH:31][C:30]=1B1OC(C)(C)C(C)(C)O1.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[C:30]1[CH:31]=[CH:32][C:33]2[O:34][CH2:35][CH2:36][NH:37][C:38]=2[C:29]=1[Cl: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 595786245-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazineHCID 86691589HCID 86691589, 화합물

생성물 1

HCID 71258189Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
90 °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 (400 mg, 0.817 mmol), 5-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (prepared according to the procedure described in WO 2009/062285; 290 mg, 0.981 mmol) and 2N Na2CO3 (0.817 mL, 1.635 mmol) in DMF (8 mL) was degassed for 15 min. Tetrakis(triphenylphosphine)palladium(0) (66.1 mg, 0.057 mmol) was added and the degassing was continued for another 5 min. The mixture was then heated at 90° C. for 16 h. At this point LCMS indicated completion of reaction and presence of desired product. After cooling to room temperature, water was added (25 mL) and the mixture was extracted with ethyl acetate (2×100 mL), washed with brine (100 mL), dried (Na2SO4), filtered and concentrated. The crude was purified by biotage (5-70% EtOAc/hexane) to afford ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (315 mg, 0.593 mmol, 72.6% yield) as a mixture of two atrope isomers which are not separable (approx 10-15% of minor atrope isomer present by LCMS and NMR). Mixture was used as is in the next step without further purification.

후처리

  1. customprepared

출처 및 근거

ORD 기록
ord-023333367f964c098cd56fc6ea271a19
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791108B2

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