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Diisopropylethylamine → (R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525654
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HRID 525654 반응식
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].ClC1[C:25](Cl)=[N:26][CH:27]=[C:28](C=1)[C:29]([OH:31])=O.N1CC[C@@H](O)C1.CCN(C(C)C)C(C)C>CC(O)C>[Cl:1][C:2]1[C:3]([N:26]2[CH2:27][CH2:28][C@@H:29]([OH:31])[CH2:25]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2479875,6-Dichloronicotinic acidHCID 2759337(R)-3-PyrrolidinolHCID 81946485,6-dichloro-N-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide

생성물 1

HCID 89907107(R)-5-chloro-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

시약·촉매·용매 1

HCID 3776
Isopropanol
용매

실험 절차

A mixture of 5,6-dichloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (prepared from 5,6-dichloronicotinic acid in an analogous fashion to that described in Stage 6.2, 1.5 g, 4.27 mmol) and (R)-pyrrolidin-3-ol (447 mg, 5.13 mmol), iPrOH (10 mL) and DIPEA (1.104 g, 8.54 mmol) were subjected to MW irradiation at 140° C. for 60 min. The RM was quenched with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered and the filtrate was evaporated off under reduced pressure to afford the title compound as a beige powder. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.85-1.97 (m, 2H) 3.59 (d, J=12 Hz, 1H) 3.7-3.8 (m, 1H) 3.8-3.95 (m, 2H) 4.35-4.40 (m, 1H) 5.00 (s, 1H) 7.35 (d, J=2 Hz, 2H) 7.86 (d, J=2 Hz, 2H) 8.17 (s, 1H) 8.66 (s, 1H) 10.22 (s, 1H).

후처리

  1. customwere subjected to MW irradiation at 140° C. for 60 min
  2. customThe RM was quenched with water (100 mL)
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic extracts were washed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated off under reduced pressure

출처 및 근거

ORD 기록
ord-668667f217364281b85a0300e3018fb9
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09340537B2

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