Glycolic Acid → (S,S)-1-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-2-hydroxy-ethanone

HRID 384512ノート

反応式

HRID 384512 の反応式
Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][N:3]2[CH2:9][C:10]1[CH:25]=[CH:24][C:13]([O:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:12][CH:11]=1.[C:26](O)(=[O:29])[CH2:27][OH:28].Cl.CN(C)CCCN=C=NCC.CCN(CC)CC>C(Cl)Cl>[S:16]1[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[N:19]=[C:15]1[O:14][C:13]1[CH:12]=[CH:11][C:10]([CH2:9][N:3]2[CH2:4][C@@H:5]3[CH2:8][C@H:2]2[CH2:7][N:6]3[C:27](=[O:28])[CH2:26][OH:29])=[CH:25][CH:24]=1

参加物

6

反応物 4

HCID 757Glycolic AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67207143(S,S)-2-[4-(2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl)-phenoxy]-benzothiazole hydrochloride

生成物 1

HCID 67206856(S,S)-1-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-2-hydroxy-ethanone収率 55.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred suspension of (S,S)-2-[4-(2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl)-phenoxy]-benzothiazole hydrochloride (1.6 g, 3.9 mmol), glycolic acid (600 mg, 7.8 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 g, 7.8 mmol) in CH2Cl2 (15 mL) was added Et3N (2.7 mL, 19.5 mmol). The resulting solution was then stirred at rt for 16 h. The resulting white suspension was partitioned between CH2Cl2 (600 mL) and satd. aq. NaHCO3 (100 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (0% to 5% CH3OH in CH2Cl2) afforded the title compound as a white solid (853 mg, 55%). MS (ESI): mass calcd. for C21H21N3O3S, 395.13; m/z found, 396.2 [M+H]+. 1H NMR (500 MHz, CDCl3, mixture of rotamers): 7.73 (d, J=8.5 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.41 (m, 2H), 7.38 (m, 1H), 7.32 (br m, 2H), 7.28 (m, 1H), 4.83 (br m, 0.5H), 4.21 (br d, J=14.5 Hz, 0.5H), 4.10-3.99 (br m, 2H), 3.80 (br d, J=11.7 Hz, 0.5H), 3.76 (d, J=13.8 Hz, 2H), 3.61 (br s, 1H), 3.50 (br s, 0.5H), 3.48-3.45 (m, 0.5H), 3.42 (br s, 0.5H), 3.39-3.35 (m, 0.5H), 3.23 (dd, J=9.2, 2.3 Hz, 0.5H), 3.01 (dd, J=9.7, 2.1 Hz, 0.5H), 2.90 (dd, J=9.8, 2.2 Hz, 0.5H), 2.81-2.77 (m, 0.5H), 2.58 (dd, J=9.7, 1.2 Hz, 0.5H), 2.07-2.01 (m, 0.5H), 2.00-1.96 (m, 0.5H), 1.80 (d, J=9.8 Hz, 0.5H), 1.70 (d, J=10.0 Hz, 0.5H).

後処理

  1. customThe resulting white suspension was partitioned between CH2Cl2 (600 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel flash chromatography (0% to 5% CH3OH in CH2Cl2)

出典と根拠

ORDレコード
ord-a445621d836b42709bd4a716f071f42f
出典データセット
uspto-grants-2013_02
特許番号
US08367719B2

反応ノート

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