Phosgene → 4-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid benzyl-hydroxy-amide

HRID 1592554노트

반응식

HRID 1592554 반응식
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:33](Cl)(Cl)=[O:34].Cl.[CH2:38]([NH:45][OH:46])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1(C)C=CC=CC=1>[CH2:38]([N:45]([OH:46])[C:33]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:8][C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:11][CH2:12]1)=[O:34])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

참가 물질

6

반응물 4

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2회HCID 11332622N-benzylhydroxylamine hydrochlorideHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

생성물 1

HCID 589972414-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid benzyl-hydroxy-amide수율 77%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a solution of COMPOUND 249 (0.115 g, 0.37 mmol) in toluene (4 mL) was added DIPEA (0.16 mL, 0.92 mmol) followed by phosgene solution (20% in toluene, 0.20 mL, 0.44 mmol). The resultant mixture was stirred at room temperature for 90 minutes then concentrated under reduced pressure. The residue was dissolved in DMF (4 mL) and treated with DIPEA (0.60 mL, 3.44 mmol) followed by N-benzylhydroxylamine hydrochloride (0.194 g, 1.22 mmol) and the resultant mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was partitioned between CH2Cl2 (50 mL) and saturated aqueous NaHCO3 (15 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 25:1:1 CH2Cl2-MeOH—NH4OH) provided 131 mg (74%) of COMPOUND 272 as a white solid. 1H NMR (CDCl3) δ 1.64-1.76 (m, 2H), 1.918-1.96 (m, 2H), 2.08 (s, 6H), 2.68-2.79 (m, 3H), 3.81 (s, 4H), 4.20 (d, 2H, J=13.2 Hz), 4.30 (s, 2H), 6.81 (s, 1H), 7.08 (dd, 2H, J=7.5, 4.8 Hz), 7.27-7.38 (m, 7H), 8.32 (d, 2H, J=3.6 Hz); 13C NMR (CDCl3) δ 18.35, 27.54, 46.12, 54.86, 57.74, 59.70, 122.87, 127.94, 128.68, 129.35, 133.88, 136.61, 138.59, 146.15, 157.28, 164.68; ES-MS m/z 460 (M+H). Anal. Calcd. For C27H33N5O2.0.2CH2Cl2: C, 68.55; H, 7.06; N, 14.70. Found: C, 68.85; H, 7.21; N, 14.79.

후처리

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DMF (4 mL)
  3. concentrationThe mixture was concentrated
  4. customthe residue was partitioned between CH2Cl2 (50 mL) and saturated aqueous NaHCO3 (15 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with CH2Cl2 (3×15 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. concentrationconcentrated
  9. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 25:1:1 CH2Cl2-MeOH—NH4OH)

출처 및 근거

ORD 기록
ord-2abe6ad753634465839ade4191a1e10c
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291631B2

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