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

HRID 1630319ノート

反応式

HRID 1630319 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].[F:28][C:29]1[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:31][C:32]2[NH:37][CH2:36][CH2:35][O:34][C:33]=2[CH:38]=1.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[C:29]([F:28])=[CH:38][C:33]2[O:34][CH2:35][CH2:36][NH:37][C:32]=2[CH:31]=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 10340Sodium CarbonateHCID 595785667-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazineHCID 86691589HCID 86691589、化合物

生成物 1

HCID 71259455Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °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 (300 mg, 0.613 mmol), 7-fluoro-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; 205 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 added and the degassing was continued for another 5 min. The mixture was then heated at 100° 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 (50 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 then purified by prep-HPLC to afford ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (approx 10-15% of minor atrope isomer present by LCMS and NMR). 1H NMR (500 MHz, CDCl3) δ 7.11 (s, 1H), 6.74 (dd, J=8.3, 1.8 Hz, 2H), 5.17 (s, 1H), 4.48-4.33 (m, 4H), 4.24 (t, J=7.0 Hz, 2H), 3.83 (br. s., 1H), 3.51-3.41 (m, 2H), 2.70 (s, 3H), 1.43-1.39 (m, 3H), 1.31-1.26 (m, 3H), 1.05 (s, 9H). LCMS (M+H)=515.4.

後処理

  1. customprepared

出典と根拠

ORDレコード
ord-f789b7dde507460eadb0ded254d89d72
出典データセット
uspto-grants-2014_07
特許番号
US08791108B2

反応ノート

読み込み中…