Dichloromethane → (S)-4-(2-chloro-9-ethyl-8-(pyrimidin-5-yl)-9H-purin-6-yl)-3-methylmorpholine

HRID 2063375노트

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HRID 2063375 반응식
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7](I)[N:8]2[CH2:11][CH3:12])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[N:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][CH:32]=[N:33][CH:34]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].ClCCl>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:29]3[CH:30]=[N:31][CH:32]=[N:33][CH:34]=3)[N:8]2[CH2:11][CH3:12])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[N:3]=1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 4192667Pyrimidine-5-boronic acid, pinacol esterHCID 58222524(S)-4-(2-chloro-9-ethyl-8-iodo-9H-purin-6-yl)-3-methylmorpholine

생성물 1

HCID 58222540(S)-4-(2-chloro-9-ethyl-8-(pyrimidin-5-yl)-9H-purin-6-yl)-3-methylmorpholine수율 77.8%

시약·촉매·용매 2

HCID 24290Palladium Chloride촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매

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온도
120 °C

실험 절차

In a 5-mL microwave vessel equipped with a stirbar was placed (S)-4-(2-chloro-9-ethyl-8-iodo-9H-purin-6-yl)-3-methyl-morpholine (30 mg, 0.074 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (22.7 mg, 0.110 mmol, 1.5 eq.), potassium phosphate (46.9 mg, 0.22 mmol, 3.0 eq.), 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (1:1) (3.0 mg, 0.0037 mmol, 0.05 eq.), and degassed 1,4-dioxane (3.0 mL). The microwave tube was capped, and the reaction mixture was heated under microwave irradiation (300 watts, 120° C.) for 15 minutes. The reaction mixture was diluted with ethyl acetate (10 mL) and filtered through a pad of Celite. 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 100% ethyl acetate in heptane) to give the desired compound (k-1) as a foam (20.6 mg, 77.8%). 1H NMR (CDCl3, 400 MHz) δ ppm 9.34 (s, 1H), 9.13 (s, 2H), 6.00 to 4.60 (broad s, 2H), 4.42 to 4.28 (m, 2H), 4.11 to 3.97 (m, 1H), 3.87 to 3.72 (m, 2H), 3.71 to 3.59 (m, 1H), 3.59 to 3.40 (broad s, 1H), 1.51 to 39 (m, 6H); LC-MS m/z (method A): RT=2.21 min, [M+H]+=360.

후처리

  1. customIn a 5-mL microwave vessel equipped with a stirbar
  2. customdegassed 1,4-dioxane (3.0 mL)
  3. customThe microwave tube was capped
  4. additionThe reaction mixture was diluted with ethyl acetate (10 mL)
  5. filtrationfiltered through a pad of Celite
  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 100% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-b3d085999be648059b512625393b0c95
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288381B2

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