Diisopropylethylamine → HCID 58777580, 화합물

HRID 1371734노트

반응식

HRID 1371734 반응식
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([F:16])=[C:14]([F:17])[CH:13]=[C:12]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C:11]=2[O:26][CH3:27])=[O:9])=[CH:6][N:5]=[C:4](Cl)[N:3]=1.FC(F)(F)C(O)=O.[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][CH:43]([NH2:46])[CH2:42][CH2:41]1)(=[O:39])=[O:38].C(N(C(C)C)CC)(C)C>C(O)C>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([F:16])=[C:14]([F:17])[CH:13]=[C:12]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C:11]=2[O:26][CH3:27])=[O:9])=[CH:6][N:5]=[C:4]([NH:46][CH:43]2[CH2:44][CH2:45][N:40]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:41][CH2:42]2)[N:3]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 11975076[1-(Methylsulfonyl)piperidin-4-yl]amine trifluoroacetateHCID 21070551(4-Amino-2-chloro-pyrimidin-5-yl)-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone

생성물 1

HCID 58777580HCID 58777580, 화합물수율 60%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To a solution of (4-amino-2-chloro-pyrimidin-5-yl)-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone (860 mg, 2.0 mmol, Example 269) in ethanol (12 mL) was added 1-methanesulfonyl-piperidin-4-ylamine trifluoroacetate salt (613.8 mg, 2.1 mmol, Example 162) and diisopropylethylamine (1.2 mL, 6.889 mmol). The mixture was heated at reflux for 4 hours and then concentrated to dryness. The residue was dissolved in ethyl acetate (20 mL). The solution was washed with brine (1×10 mL) and dried over anhydrous magnesium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with 45–60% ethyl acetate in hexanes) yielded [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone as white glass (684 mg, 60%). LR-MS (M+) 572.1.

후처리

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hours
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
  5. washThe solution was washed with brine (1×10 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe solids were filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customPurification of the crude residue
  10. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with 45–60% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-7dee964d4c834dc8939cac8604c4484d
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07157455B2

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