Triethylamine → N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-furan-2-ylbenzoxazole-4-carboxamide

HRID 506307노트

반응식

HRID 506307 반응식
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]2[C:9](=[C:11]([C:15]([OH:17])=O)[CH:12]=[CH:13][CH:14]=2)[N:10]=1.Cl.Cl.[NH2:20][CH:21]1[CH2:28][CH:27]2[N:29]([CH3:30])[CH:23]([CH2:24][CH2:25][CH2:26]2)[CH2:22]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>[CH3:30][N:29]1[CH:23]2[CH2:24][CH2:25][CH2:26][CH:27]1[CH2:28][CH:21]([NH:20][C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:8]3[O:7][C:6]([C:2]4[O:1][CH:5]=[CH:4][CH:3]=4)=[N:10][C:9]=13)=[O:17])[CH2:22]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 684568872-Furan-2-ylbenzoxazole-4-carboxylic acid

생성물 1

HCID 11494326N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-furan-2-ylbenzoxazole-4-carboxamide수율 61%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 2-furan-2-ylbenzoxazole-4-carboxylic acid (51 mg, 0.22 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (59 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (59 mg, 0.31 mmol) and 1-hydroxybenzotriazole (84 mg, 0.62 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then triethylamine (0.14 mL, 1.1 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. 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 (2×50 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)-2-furan-2-ylbenzoxazole-4-carboxamide (49 mg, 61%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 8.94 (d, J=6.0 Hz, 1H), 8.22 (dd, J=7.5, 1.0 Hz, 1H), 7.74 (d, J=1.5 Hz, 1H), 7.68 (dd, J=8.0, 1.0 Hz, 1H), 7.46 (t, J=4.0 Hz, 1H), 7.35 (d, J=4.0 Hz, 1H), 6.79-6.66 (m, 1H), 4.58-4.53 (m, 1H), 3.12 (d, J=10.0 Hz, 2H), 2.66-2.59 (m, 2H), 2.55 (s, 3H), 2.18-1.98 (m, 3H), 1.68-1.49 (m, 3H), 1.22-1.17 (m, 2H); MS (ESI+) m/z 366 (M+H); HPLC>99% (AUC), tR=12.12 min.

후처리

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×50 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-a4f5e18c095142bc9db05cf2b2b20777
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781430B2

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