Diisopropylethylamine → HCID 178433216, 화합물

HRID 241459노트

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HRID 241459 반응식
C([O-])=O.[CH3:4][C:5]1[N:6]=[C:7]([NH3+:20])[NH:8][C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.[C:21]([O:25][C:26]([NH:28][CH2:29][C:30]1[CH:31]=[C:32]([C:39](O)=[O:40])[C:33]([CH:36]([F:38])[F:37])=[N:34][CH:35]=1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.O>[F:38][CH:36]([F:37])[C:33]1[N:34]=[CH:35][C:30]([CH2:29][NH:28][C:26](=[O:27])[O:25][C:21]([CH3:22])([CH3:23])[CH3:24])=[CH:31][C:32]=1[C:39](=[O:40])[NH:20][C:7]1[NH:8][C:9]([C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:19])([F:17])[F:18])=[CH:14][CH:15]=2)=[C:5]([CH3:4])[N:6]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2회HCID 710606065-[(Tert-butoxycarbonylamino)methyl]-2-(difluoromethyl)pyridine-3-carboxylic acidHCID 178433220HCID 178433220, 화합물

생성물 1

HCID 178433216HCID 178433216, 화합물수율 56.5%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
60 °C

실험 절차

Dissolve [4-methyl-5-[4-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]ammonium formate (0.205 g, 0.714 mmol) and 5-[(tert-butoxycarbonylamino)methyl]-2-(difluoromethyl)pyridine-3-carboxylic acid (0.283 g, 0.749 mmol) in DCM (5 mL). Add DIPEA (0.50 mL, 2.855 mmol) followed by BOP (0.350 g, 0.792 mmol). Heat the mixture to 60° C., and stir 16 hours. Add benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.150 g, 0.339 mmol). Stir the mixture for 2 hours. Pour the reaction mixture into water (15 mL). Extract with EtOAc (3×15 mL, and sequentially wash the combined organics with a saturated sodium chloride aqueous solution (4×15 mL) and a saturated sodium bicarbonate aqueous solution (15 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify the residue by reverse phase flash chromatography (Analogix® 55 g @ 40 mL/min) eluting with a gradient of 5-75% ACN/water over 30 minutes. Concentrate the appropriate fractions under reduced pressure until only water remains and the product is a suspended solid. Add a saturated NaHCO3 aqueous solution (50 mL), and extract with EtOAc (2×30 mL) to give the title compound (0.212 g, 56%) as a white solid. LCMS (m/z) 526 (M+1) 524 (M−1).

후처리

  1. stirringStir the mixture for 2 hours
  2. extractionExtract with EtOAc (3×15 mL
  3. washsequentially wash the combined organics with a saturated sodium chloride aqueous solution (4×15 mL)
  4. dry with materialDry the organic extracts over sodium sulfate
  5. filtrationfilter
  6. customcollect the filtrate
  7. concentrationand concentrate the filtrate under reduced pressure
  8. customPurify the residue by reverse phase flash chromatography (Analogix® 55 g @ 40 mL/min)
  9. washeluting with a gradient of 5-75% ACN/water over 30 minutes
  10. concentrationConcentrate the appropriate fractions under reduced pressure until only water
  11. additionAdd a saturated NaHCO3 aqueous solution (50 mL)
  12. extractionextract with EtOAc (2×30 mL)

출처 및 근거

ORD 기록
ord-44e1defacc1442f7adeb2432ad9e4f8d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648200B2

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