Triethylamine → (S)-2-cyclopropyl-N-(quinuclidin-3-yl)benzo[d]oxazole-4-carboxamide

HRID 1987964

反応式

HRID 1987964 の反応式
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:13]([OH:15])=O)[CH:10]=[CH:11][CH:12]=3)[N:8]=2)[CH2:3][CH2:2]1.Cl.Cl.[NH2:18][C@H:19]1[CH:24]2[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]2)[CH2:20]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:21]12[CH2:26][CH2:25][CH:24]([CH2:23][CH2:22]1)[C@H:19]([NH:18][C:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:6]3[O:5][C:4]([CH:1]4[CH2:2][CH2:3]4)=[N:8][C:7]=13)=[O:15])[CH2:20]2

参加物

8

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 689999402-Cyclopropylbenzoxazole-4-carboxylic acid

生成物 1

HCID 24178536(S)-2-cyclopropyl-N-(quinuclidin-3-yl)benzo[d]oxazole-4-carboxamide収率 43.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 2-cyclopropylbenzoxazole-4-carboxylic acid (65 mg, 0.32 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (64 mg, 0.32 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123 mg, 0.64 mmol) and 1-hydroxybenzotriazole (86 mg, 0.64 mmol) in DMF (2 mL) was stirred at room temperature for 5 min, then triethylamine (0.17 mL, 1.28 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with dichloromethane (20 mL), then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-cyclopropylbenzoxazole-4-carboxamide (43 mg, 43%) as a colorless semisolid: 1H NMR (500 MHz, CDCl3) δ 9.43 (d, J=7.0 Hz, 1H), 8.10 (dd, J=7.5, 1.0 Hz, 1H), 7.56 (dd, J=8.0, 2.0 Hz, 1H), 7.36 (t, J=8.5 Hz, 1H), 4.28-4.22 (m, 1H), 3.49 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.10-2.85 (m, 4H), 2.75 (dd, J=14.0, 4.5 Hz, 1H), 2.28-2.20 (m, 1H), 2.12-2.06 (m, 1H), 2.00-1.90 (m, 1H), 1.75-1.69 (m, 2H), 1.60-1.50 (m, 1H), 1.35-1.22 (m, 4H); MS (ESI+) m/z 312 (M+H); HPLC>99% (AUC), tR=12.31 min.

後処理

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 12 h
  3. washwashed with a saturated solution of sodium bicarbonate (10 mL)
  4. extractionThe aqueous layer was further extracted with dichloromethane (3×15 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, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide)

出典と根拠

ORDレコード
ord-2d674c38046542f3b09ab9ea603c93f7
出典データセット
uspto-grants-2009_06
特許番号
US07553846B2

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