2-Bromo-N,N-dimethylacetamide → 7-N-(tert-Butoxycarbonyl)-8-[2-(dimethylamino)-2-oxoethyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

HRID 133080ノート

反応式

HRID 133080 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].Br[CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32]>O1CCCC1.CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[N:16]=[C:10]2[CH:9]1[CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32])=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 3

HCID 2255442-Bromo-N,N-dimethylacetamideHCID 2724682Lithium diisopropylamideHCID 53393358tert-Butyl 2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazine-7(8H)-carboxylate

生成物 1

HCID 693632797-N-(tert-Butoxycarbonyl)-8-[2-(dimethylamino)-2-oxoethyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
-78 °C

実験手順

To a solution of 2.13 g (7.30 mmol) of 7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (Example 2, Step A) in 10 mL of tetrahydrofuran at −78° C. was added lithium diisopropylamide (4.02 mL of a 2.0M solution in heptane/tetrahydrofuran/ethylbenzene, 8.03 mmol). The mixture was allowed to stir at −78° C. for 15 min, and then 2-bromo-N,N-dimethylacetamide from Step A in 5 mL of tetrahydrofuran was added, and the mixture slowly warmed to ambient temperature over 18 h. The reaction was quenched with aqueous ammonium chloride and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated. Purification by flash chromatography (silica gel, gradient of 50% to 75% ethyl acetate/hexane) yielded the title compound. LC/MS 322 ((M+1)-t-butyl).

後処理

  1. temperaturethe mixture slowly warmed to ambient temperature over 18 h
  2. customThe reaction was quenched with aqueous ammonium chloride
  3. extractionthe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, gradient of 50% to 75% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-afcf7d6503a34e199fae461b24d58255
出典データセット
uspto-grants-2008_06
特許番号
US07390809B2

反応ノート

読み込み中…