1,2-Dimethoxyethane → 6'-(Hydroxymethyl)-2-morpholino-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 923986

반응식

HRID 923986 반응식
Br[C:2]1[C:3]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]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].[OH:28][CH2:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCO.O>[OH:28][CH2:29][C:30]1[N:35]=[CH:34][C:33]([C:2]2[C:3]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:19])([F:20])[F:18])=[CH:12][CH:11]=3)=[O:8])[CH:21]=2)=[CH:32][CH:31]=1

참가 물질

8

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 441182556-(Hydroxymethyl)pyridine-3-boronic acidHCID 899067015-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide

생성물 1

HCID 1181952626'-(Hydroxymethyl)-2-morpholino-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

5-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 148.1, 60 mg, 0.134 mmol), (6-(hydroxymethyl)pyridin-3-yl)boronic acid (41.1 mg, 0.269 mmol), Pd(PPh3)2Cl2 (9.44 mg, 0.013 mmol) and Na2CO3 (42.8 mg, 0.403 mmol) were added to a MW vial and treated with a mixture of DME (570 μL), water (163 μL) and EtOH (81 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min and then at 130° C. for 20 min, diluted with DME (2 mL) and treated with Si-Thiol (Silicycle, 1.44 mmol/g, 46.7 mg, 0.067 mmol). The RM was centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column 2-EP, from 15% to 20% in 6 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=0.95 min, m/z=475.4 [M+H]+, m/z=473.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.07-3.22 (m, 4H) 3.48-3.62 (m, 4H) 4.63 (s, 2H) 5.54 (br. s, 1H) 7.38 (d, J=8.53 Hz, 2H) 7.60 (d, J=8.03 Hz, 1H) 7.82-7.92 (m, 2H) 8.11 (d, J=8.28 Hz, 1H) 8.13-8.16 (m, 1H) 8.75-8.79 (m, 1H) 8.79-8.86 (m, 1H) 10.38 (br. s, 1H).

후처리

  1. customThe vial was sealed
  2. customevacuated/purged with argon
  3. customsubjected to MW irradiation at 125° C. for 20 min
  4. additiondiluted with DME (2 mL)
  5. filtrationthe supernatant was filtered
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a residue which
  8. customwas purified by preparative SFC (Column 2-EP, from 15% to 20% in 6 min)

출처 및 근거

ORD 기록
ord-2f71f8c7cd7e43d7ae3d7719568ca3bd
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278981B2

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