t-Butyl bromide → Tert-butyl 1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylate

HRID 710940

반응식

HRID 710940 반응식
[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:19]=[C:20]([C:22]3([C:25]([OH:27])=[O:26])[CH2:24][CH2:23]3)[N:21]=2)[C:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[O:13][CH2:12]3)=[CH:7][CH:8]=1.[C:28](Br)([CH3:31])([CH3:30])[CH3:29].C([O-])([O-])=O.[K+].[K+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C=O)C>[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:19]=[C:20]([C:22]3([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]3)[N:21]=2)[C:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[O:13][CH2:12]3)=[CH:7][CH:8]=1

참가 물질

6

반응물 3

HCID 10485t-Butyl bromide2회HCID 11430Potassium Carbonate2회HCID 686549441-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

생성물 1

HCID 71612117Tert-butyl 1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylate

시약·촉매·용매 2

HCID 66133Benzyl triethylammonium chloride촉매HCID 6228Dimethylformamide용매

반응 조건

온도
55 °C

실험 절차

A suspension of 1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylic acid (30 mg, 83 μmol) and benzyltriethyl-ammonium chloride (19 mg, 83 μmol) in DMF (1.0 mL) was gently heated until it became a solution. Tert-butyl bromide (297 μL, 2.64 mmol) and K2CO3 (171 mg, 1.24 mmol) were added and the mixture was stirred at 55° C. for three days. Additional tert-butyl bromide (139 μL, 1.24 mmol) and K2CO3 (171 mg, 1.24 mmol) were added and the mixture was stirred at 55° C. for one more day. PrepHPLC purification afforded the title compound. HPLC-Retention time (XE Metode 7 CM): 2.29 minutes. Detected “M+1”-mass: 422.18. Calculated “M+1”-mass: 422.17. 1H NMR (DMSO, 300 MHz): δ=8.27-8.22 (m, 1H), 8.16 (dd, 1H, 3=8.0, 1.5 Hz), 8.00 (d, 1H, J=8.2 Hz), 7.40 (d, 1H, J=8.2 Hz), 7.22 (d, 1H, J=8.3 Hz), 5.51 (s, 2H), 4.04 (s, 3H), 1.54-1.40 (m, 4H), 1.38 (s, 9H) ppm.

후처리

  1. temperaturewas gently heated until it
  2. stirringthe mixture was stirred at 55° C. for one more day
  3. customPrepHPLC purification

출처 및 근거

ORD 기록
ord-aa78d4d184b641b399da53bc3a829e6e
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181248B2

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