Dimethylformamide → 5-bromo-2,4-dimethoxy-N-(1-(pyridin-2-yl)cyclopropyl)benzamide

HRID 1688269

반응식

HRID 1688269 반응식
[Br:1][C:2]1[C:3]([O:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C=O)C.C([N:23](CC)[CH:24]([CH3:26])[CH3:25])(C)C.CN(C(ON1N=N[C:39]2[CH:40]=[CH:41][CH:42]=[N:43][C:38]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(OCC)C>[Br:1][C:2]1[C:3]([O:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([NH:23][C:24]1([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][N:43]=2)[CH2:26][CH2:25]1)=[O:9]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 135050975-Bromo-2,4-dimethoxybenzoic acid

생성물 1

HCID 672115435-bromo-2,4-dimethoxy-N-(1-(pyridin-2-yl)cyclopropyl)benzamide수율 106%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

To a 2 dram vial was added 5-bromo-2,4-dimethoxybenzoic acid (1.044 g, 4 mmol), DMF (48.2 mL), N,N-Diisopropylethylamine (2.79 mL, 16.00 mmol), 1-(pyridin-2-yl)cyclopropanamine, 2HCl (0.911 g, 4.40 mmol), and finally HATU (2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethyl isouronium hexafluorophosphate(V), 6.08 g, 16.00 mmol). The vial was capped and shaken for 16 hours at room temperature. The crude reaction mixture was diluted with 10 mL of DCM, washed with 5 mL of 1M HCl, extracted, washed with 20 mL of brine, and dried over magnesium sulfate. The solution was pushed through a plug of silica gel and evaporated to dryness. Trituration with 20 mL of diethyl ether gave 1.6 grams of 5-bromo-2,4-dimethoxy-N-(1-(pyridin-2-yl)cyclopropyl)benzamide as a tan solid (76% yield). 1H NMR (400 MHz, THF-d8) δ ppm 1.22-1.32 (m, 2H), 1.59-1.67 (m, 2H), 3.94 (s, 3H), 4.02 (s, 3H), 6.72 (s, 1H), 7.09 (m, 1H), 7.47 (d, J=8.03 Hz, 1H), 7.62 (td, J=7.72, 1.88 Hz, 1H), 8.20 (s, 1H), 8.39-8.52 (m, 2H). LCMS Rt=2.162 min., m/z 379.2 (M+2H), 96% purity.

후처리

  1. customThe vial was capped
  2. customThe crude reaction mixture
  3. washwashed with 5 mL of 1M HCl
  4. extractionextracted
  5. washwashed with 20 mL of brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness

출처 및 근거

ORD 기록
ord-d0373316664543ff97486e8d5bc02209
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148382B2

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