Azidomethyl 2,2-dimethylpropanoate → (4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate

HRID 2060723노트

반응식

HRID 2060723 반응식
[C:1]([O:7][CH2:8][N:9]=[N+:10]=[N-:11])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[C:12]([C:14]1[CH:19]=[C:18]([O:20][C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=2)[CH:17]=[CH:16][N:15]=1)#[CH:13].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(O)(C)(C)C.O.CCOC(C)=O.S([O-])([O-])(=O)=O.[Cu+2]>[C:1]([O:7][CH2:8][N:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=3)[CH:17]=[CH:16][N:15]=2)[N:11]=[N:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

참가 물질

8

반응물 3

HCID 11521126Azidomethyl 2,2-dimethylpropanoateHCID 23667548Sodium AscorbateHCID 598255834-(2-Ethynylpyridin-4-yloxy)-2-fluorobenzenamine

생성물 1

HCID 67399290(4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate수율 90%

시약·촉매·용매 4

HCID 24462Copper Sulfate촉매HCID 962Water용매3회HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of azidomethyl pivalate (0.075 g, 0.477 mmol), 4-(2-ethynylpyridin-4-yloxy)-2-fluorobenzenamine from Example A21 (0.109 g, 0.477 mmol) in t-butanol (0.6 mL) and water (0.6 mL) was added sodium ascorbate (0.021 g, 0.095 mmol). Copper(II)sulfate in water (0.048 ml, 0.048 mmol) was added to the above suspension and the dark red mixture was stirred for 3 h at RT. It was diluted with water (30 mL) and EtOAc (20 mL), the layers were separated and the aqueous layer was extracted with EtOAc (2×15 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated to afford (4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate as a red solid. (0.165 g, 90% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.54 (s, 1H), 8.46 (brs, 1H), 7.60 (s, 1H), 6.98 (d, J=8.8 Hz, 1H), 6.94 (d, J=3.6 Hz, 1H), 6.83-6.81 (m, 2H), 6.42 (s, 2H), 4.78 (s, 2H), 1.17 (s, 9H); MS (ESI) m/z: 386.1 (M+H+).

후처리

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×15 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-dc6bc1a26600452c8cac5fabd7381752
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278331B2

반응 노트

불러오는 중…