Tetrahydrofuran → 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

HRID 1668952노트

반응식

HRID 1668952 반응식
[CH3:1][C:2]1[C:11]([NH2:12])=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl[C:25]1[C:30]([C:31]2[N:36]=[CH:35][N:34]=[C:33]([NH:37][CH3:38])[CH:32]=2)=[CH:29][CH:28]=[CH:27][N:26]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>O.C(OCC)(=O)C.O1CCOCC1>[CH3:1][C:2]1[C:11]([NH:12][C:25]2[C:30]([C:31]3[CH:32]=[C:33]([NH:37][CH3:38])[N:34]=[CH:35][N:36]=3)=[CH:29][CH:28]=[CH:27][N:26]=2)=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

참가 물질

8

반응물 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 589422526-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amineHCID 673386327-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

생성물 1

HCID 673392747-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
150 °C

실험 절차

A mixture of 7-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine (0.083 g, 0.26 mmol) and 6-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amine (0.058 g, 0.26 mmol) were placed in a clear microwave vial along with 3 ml of dioxane. While stirring, lithium bis(trimethylsilyl)amide in THF (1.6 ml, 1.6 mmol) was added dropwise with a syringe to the reaction. The vial was capped and heated in a Personal Chemistry SmithSynthesizer to 150° C. for 12 minutes. The reaction was diluted with water and ethyl acetate. The organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The residue was purified by HPLC using a gradient of 5% ACN 0.1% TFA to 95% ACN 0.1% TFA in water 0.1% TFA. The pure fractions were neutralized with ammonium hydroxide and the volatiles were removed under reduced pressure. The solid that crashed out of the aqueous layer was filtered off, washed with water and dried in a vacuum oven at 45 degrees to give 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine as a light yellow solid. MS (M+H)+ 474.

후처리

  1. customThe vial was capped
  2. washThe organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  3. customThe residue was purified by HPLC
  4. customthe volatiles were removed under reduced pressure
  5. filtrationwas filtered off
  6. washwashed with water
  7. customdried in a vacuum oven at 45 degrees

출처 및 근거

ORD 기록
ord-0ca10247e129449ead9eab1562734063
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989461B2

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