Tetrahydrofuran → (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 574335ノート

反応式

HRID 574335 の反応式
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C:22](=[O:27])[C:23]([O:25][CH3:26])=[O:24].CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24]

参加物

7

反応物 3

HCID 8028TetrahydrofuranHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole tolueneHCID 86670287Methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

生成物 1

HCID 86670288(S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate収率 88.2%

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
-35 °C

実験手順

To a stirred yellow solution of methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (1 g, 2.61 mmol) in anhydrous toluene (25 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.947 mL, 1.042 mmol). The mixture was cooled to −35° C. and a solution of 1M catechoborane/THF (3.65 mL, 3.65 mmol) was added over 10 min. After 30 min, the reaction mixture was slowly warmed to −15 C and stirred for additional 30 min. and diluted with EtOAc (30 mL) and sat. Na2CO3 (10 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by silica gel chromatography (5-70% EtOAc/hexane) to afford desired (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (888 mg, 2.301 mmol, 88% yield) as off-white solid. EE=95.4% 1H NMR (500 MHz, CDCl3) δ 7.77-7.71 (m, 2H), 7.19 (d, J=7.6 Hz, 1H), 6.93 (s, 1H), 5.78 (d, J=2.7 Hz, 1H), 3.86 (s, 3H), 3.56 (d, J=2.7 Hz, 1H), 2.89-1.81 (m, 4H), 2.64 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=386.3.

後処理

  1. temperaturethe reaction mixture was slowly warmed to −15 C
  2. stirringThe mixture was stirred vigorously for 30 min
  3. washthe organic phase washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (5-70% EtOAc/hexane)

出典と根拠

ORDレコード
ord-e926c827eb194aad97ed44906325e037
出典データセット
uspto-grants-2015_05
特許番号
US09034882B2

反応ノート

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