Dichloromethane → (S)-4-(2-chloro-8-cyclopropyl-9-methyl-9H-purin-6-yl)-3-methylmorpholine

HRID 2063363ノート

反応式

HRID 2063363 の反応式
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7](I)[N:8]2[CH3:11])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].ClCCl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:20]3[CH2:22][CH2:21]3)[N:8]2[CH3:11])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 58222526(S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholine

生成物 1

HCID 58222533(S)-4-(2-chloro-8-cyclopropyl-9-methyl-9H-purin-6-yl)-3-methylmorpholine収率 71%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

In a high-pressure vessel was placed (S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholine (78.2 mg, 0.20 mmol), cyclopropylboronic acid (25.8 mg, 0.30 mmol, 1.5 eq.), potassium phosphate (127.4 mg, 0.60 mmol, 3.0 eq.), [1,1′-bis-(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (4.9 mg, 0.006 mmol, 0.03 eq.), and 1,4-dioxane (1.0 mL). The reaction mixture was degassed for 15 minutes. The vessel tube was sealed tightly, and the reaction mixture was stirred at 100° C. After 18 h the reaction was cooled to RT and diluted with ethyl acetate. The organic layer was washed with water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane) to give the desired compound as a foam (43.7 mg, 71%). TLC (40% ethyl acetate/hexane), Rf=0.41; LC-MS m/z (method B2)=308 [M+H]+, RT=1.94 min.

後処理

  1. customIn a high-pressure vessel was placed
  2. customThe reaction mixture was degassed for 15 minutes
  3. customThe vessel tube was sealed tightly
  4. temperatureAfter 18 h the reaction was cooled to RT
  5. additiondiluted with ethyl acetate
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-40a6e5b717c74ce1ae2adaa02dcd1bfb
出典データセット
uspto-grants-2012_10
特許番号
US08288381B2

反応ノート

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