1-(Bromomethyl)-2-chloro-4-(methylsulfonyl)benzene → 2-Chloro-5-(2-chloro-4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 2169542ノート

反応式

HRID 2169542 の反応式
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][CH2:7][CH:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1.CC(C)([O-])C.[Na+].Br[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=1[Cl:34]>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][C:25]=3[Cl:34])[CH2:7][CH:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1

参加物

6

反応物 3

HCID 27610831-(Bromomethyl)-2-chloro-4-(methylsulfonyl)benzeneHCID 23676156Sodium t-butoxide2 回HCID 86670087HCID 86670087、化合物

生成物 1

HCID 866700902-Chloro-5-(2-chloro-4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine収率 37.8%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-Chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x2, 200 mg, 0.882 mmol) was dissolved in DMSO (4.4 mL). Sodium tert-butoxide (102 mg, 1.059 mmol) was then added to give a brown solution. After 5 minutes, 1-(bromomethyl)-2-chloro-4-(methylsulfonyl)benzene (250 mg, 0.882 mmol) was added dropwise. The reaction mixture was stirred for 18 hours. Additional sodium tert-butoxide (0.5 eq) was added and the reaction mixture was stirred for an additional 18 hours. The reaction mixture was subsequently diluted with ethyl acetate and was washed with aqueous saturated NH4Cl (3×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was loaded onto an ISCO® silica gel cartridge (12 g) and eluted with an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow oil (143 mg, 37%). ESI-MS m/z [M+H]+ calc'd for C17H18Cl2N4O3S, 430.3; found 431.3.

後処理

  1. customto give a brown solution
  2. stirringthe reaction mixture was stirred for an additional 18 hours
  3. washwas washed with aqueous saturated NH4Cl (3×25 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washeluted with an ethyl acetatehexane gradient
  8. customThe product was collected
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-37a78c1fdf644a8ab1866fe824ffcb3e
出典データセット
uspto-grants-2015_06
特許番号
US09045496B2

反応ノート

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