1,2-Dimethoxyethane → 3-(5-Cyano-1H-pyrrol-2-yl)-4-((3 S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 525686노트

반응식

HRID 525686 반응식
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:26][C@H:25]([OH:27])[C@@H:24]([OH:28])[CH2:23]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].C(OC([N:36]1[C:40]([C:41]#[N:42])=[CH:39][CH:38]=[C:37]1B(O)O)=O)(C)(C)C.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>[C:41]([C:40]1[NH:36][C:37]([C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=2[N:22]2[CH2:23][C@H:24]([OH:28])[C@@H:25]([OH:27])[CH2:26]2)[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:17])([F:18])[F:16])=[CH:10][CH:9]=2)=[O:6])=[CH:38][CH:39]=1)#[N:42]

참가 물질

8

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 899064793-Bromo-4-((3 S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamideHCID 89907888(1-(tert-butoxycarbonyl)-5-cyano-1H-pyrrol-2-yl)boronic acid

생성물 1

HCID 1180450023-(5-Cyano-1H-pyrrol-2-yl)-4-((3 S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
70 °C

실험 절차

3-Bromo-4-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 28.1, 100 mg, 0.217 mmol), (1-(tert-butoxycarbonyl)-5-cyano-1H-pyrrol-2-yl)boronic acid (Stage 29.1, 103 mg, 0.436 mmol), Pd(PPh3)2Cl2 (15.22 mg, 0.022 mmol), Na2CO3 (92 mg, 0.867 mmol), DME (920 μL), water (263 μL) and EtOH (131 μL) were added to a MW vial, which was sealed, evacuated/purged with argon and the RM was stirred at 70° C. for 16 h. MeOH (0.5 mL) was added and the RM was subjected to MW irradiation at 150° C. for 5 min. The RM was diluted with DME (3 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 90 mg, 0.130 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 12 g, DCM/MeOH-1% NH4OH, from 1% to 10% MeOH-1% NH4OH) followed by preparative SFC (Column NH2, from 26% to 31% in 10 min) to yield the title compound as an off-white solid. UPLC-MS (Condition 3) tR=0.99 min, m/z=473.2 [M+H]+, m/z=471.1 [M−H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.81 (d, J=10.76 Hz, 2H) 3.26-3.32 (m, 2H) 3.89 (br. s, 2H) 5.08 (d, J=2.93 Hz, 2H) 6.24 (d, J=3.67 Hz, 1H) 6.84 (d, J=8.93 Hz, 1H) 7.00 (d, J=3.67 Hz, 1H) 7.33 (d, J=8.44 Hz, 2H) 7.84-7.93 (m, 4H) 10.10 (s, 1H) 12.52 (br. s, 1H).

후처리

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionMeOH (0.5 mL) was added
  4. customthe RM was subjected to MW irradiation at 150° C. for 5 min
  5. additionThe RM was diluted with DME (3 mL)
  6. filtrationthe supernatant was filtered
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give a residue which
  9. customwas purified by flash chromatography (RediSep® Silica gel column, 12 g, DCM/MeOH-1% NH4OH, from 1% to 10% MeOH-1% NH4OH)
  10. customfollowed by preparative SFC (Column NH2, from 26% to 31% in 10 min)

출처 및 근거

ORD 기록
ord-a2ba285cd20246f392873f8c1cfea2dc
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340537B2

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