Diisopropylethylamine → 5-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxyl]methyl}-N-[(dimethylamino)sulfonyl]-2-fluorobenzamide diethylamine salt

HRID 1525653노트

반응식

HRID 1525653 반응식
[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:24][N:25]([C:27](ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.CN[N:59](NC)[SH:60](=[O:62])=[O:61]>ClCCl>[CH2:15]([NH:16][CH2:17][CH3:18])[CH3:14].[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:59][S:60]([N:25]([CH3:27])[CH3:24])(=[O:62])=[O:61])=[O:8]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896191735-Chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acidHCID 178486254HCID 178486254, 화합물

생성물 1

HCID 716161505-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxyl]methyl}-N-[(dimethylamino)sulfonyl]-2-fluorobenzamide diethylamine salt수율 18.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of 5-chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acid (Preparation 27, 200 mg, 0.56 mmol) in dichloromethane (20 mL) was added HATU (256 mg, 0.67 mmol) and diisopropylethylamine (0.30 mL, 1.79 mmol). The reaction mixture was stirred at room temperature for 15 minutes before the addition of N,N-dimethylamino sulphonamide (209 mg, 1.68 mmol). The reaction mixture was stirred under nitrogen at room temperature for 18 hours. Upon completion the reaction mixture was washed with aqueous NH4Cl (15 mL) and brine (15 mL). The organic extracts were dried (MgSO4) and evaporated under vacuum to give the crude product as an orange oil, which was purified by column chromatography on silica (eluting with 1:1 cyclohexane/EtOAc). The partially purified product was dissolved in DMSO (2 mL) and purified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid) to afford the title compound as a beige solid (28 mg, 11%).

후처리

  1. washUpon completion the reaction mixture was washed with aqueous NH4Cl (15 mL) and brine (15 mL)
  2. dry with materialThe organic extracts were dried (MgSO4)
  3. customevaporated under vacuum
  4. customto give the crude product as an orange oil, which
  5. customwas purified by column chromatography on silica (eluting with 1:1 cyclohexane/EtOAc)
  6. dissolutionThe partially purified product was dissolved in DMSO (2 mL)
  7. custompurified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid)

출처 및 근거

ORD 기록
ord-a33b2ad084164c6f8cb74874f1006e58
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085517B2

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