p-Toluenesulfonic acid monohydrate → N-(4-bromo-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842798노트

반응식

HRID 1842798 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH3:17])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Br:30][C:31]1[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][C:34]([NH2:35])=[C:33]([O:41][CH3:42])[CH:32]=1>CC(O)CCC>[Br:30][C:31]1[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][C:34]([NH:35][C:2]2[N:7]=[C:6]([C:8]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]([CH3:17])[CH:9]=3)[CH:5]=[CH:4][N:3]=2)=[C:33]([O:41][CH3:42])[CH:32]=1

참가 물질

5

반응물 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 597435953-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole2회HCID 71743100HCID 71743100, 화합물2회

생성물 1

HCID 71239107N-(4-bromo-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine수율 74%

시약·촉매·용매 1

HCID 223862-Pentanol용매

실험 절차

A solution of 3-(2-chloropyrimidin-4-yl)-1-methylindole (Intermediate 130, 0.829 g, 3.40 mmol), p-toluene sulphonic acid monohydrate (0.924 g, 4.86 mmol) and 4-bromo-2-methoxy-5-nitroaniline (Intermediate 4, 0.8 g, 3.24 mmol) was heated at reflux in 2-pentanol (32 mL) under an atmosphere of N2 for 18 h. The mixture was then allowed to cool, and was then concentrated in vacuo. The resulting residue was triturated with CH3CN until a yellow precipitate formed. This solid was collected by filtration and was washed with diethyl ether. The solid was suspended in 10% CH3OH in CH2Cl2 and washed with saturated aqueous NaHCO3 (2×) followed by water. The organic solution was then concentrated in vacuo, and the resulting residue was triturated in CH3CN/water. The mixture was then filtered, and the collected solid was washed with CH3CN followed by diethyl ether and was then air dried to give the title compound (1.082 g, 74%) as a yellow solid; 1H NMR: 3.90 (3H, s), 4.05 (3H, s), 7.15-7.21 (1H, m), 7.26-7.31 (1H, m), 7.36 (1H, d), 7.52 (1H, s), 7.56 (1H, d), 8.34 (1H, s), 8.39 (1H, s), 8.40-8.45 (2H, m), 9.20 (1H, s); m/z: ES+ MH+ 454/456.

후처리

  1. temperatureto cool
  2. concentrationwas then concentrated in vacuo
  3. customThe resulting residue was triturated with CH3CN until a yellow precipitate
  4. customformed
  5. filtrationThis solid was collected by filtration
  6. washwas washed with diethyl ether
  7. washwashed with saturated aqueous NaHCO3 (2×)
  8. concentrationThe organic solution was then concentrated in vacuo
  9. customthe resulting residue was triturated in CH3CN/water
  10. filtrationThe mixture was then filtered
  11. washthe collected solid was washed with CH3CN
  12. customair dried

출처 및 근거

ORD 기록
ord-60fad17323d64444add69705803e98b4
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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