Triethylamine → N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-p-tolylbenzoxazole-4-carboxamide

HRID 506292

반응식

HRID 506292 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3)=[N:6][C:5]2=[C:16]([C:18]([OH:20])=O)[CH:17]=1.Cl.Cl.[NH2:23][CH:24]1[CH2:31][CH:30]2[N:32]([CH3:33])[CH:26]([CH2:27][CH2:28][CH2:29]2)[CH2:25]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[CH3:33][N:32]1[CH:26]2[CH2:27][CH2:28][CH2:29][CH:30]1[CH2:31][CH:24]([NH:23][C:18]([C:16]1[CH:17]=[C:2]([Cl:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=4)=[N:6][C:5]=13)=[O:20])[CH2:25]2

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 684583386-Chloro-2-p-tolylbenzoxazole-4-carboxylic acid

생성물 1

HCID 11531928N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-p-tolylbenzoxazole-4-carboxamide수율 26.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 6-chloro-2-p-tolylbenzoxazole-4-carboxylic acid (45 mg, 0.16 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (43 mg, 0.19 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg, 0.31 mmol) and 1-hydroxybenzotriazole (43 mg, 0.31 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then triethylamine (0.07 mL, 0.63 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with ethyl acetate (20 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×22 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-p-tolylbenzoxazole-4-carboxamide (18 mg, 26%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.94 (d, J=7.3 Hz, 1H), 8.18 (d, J=1.9 Hz, 1H), 8.11 (d, J=8.2 Hz, 2H), 7.67 (d, J=1.9 Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 4.63-4.50 (m, 1H), 3.12 (d, J=10.4 Hz, 2H), 2.70-2.57 (m, 2H), 2.54 (s, 3H), 2.48 (s, 3H), 2.20-1.90 (m, 2H), 1.65-1.52 (m, 2H), 1.51-1.48 (m, 2H), 1.20-1.10 (m, 2H); MS (ESI+) m/z 424 (M+H); HPLC 95.0% (AUC), tR=13.80 min.

후처리

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 12 h
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×22 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

출처 및 근거

ORD 기록
ord-80e2a59dc98f44cd814a7ab08c6a29c0
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781430B2

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