Dicyclohexylcarbodiimide → Methyl N-((7-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate

HRID 987899ノート

反応式

HRID 987899 の反応式
[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH2:13][C:14]([OH:16])=O)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][NH:42][CH2:43][C:44]([O:46][CH2:47]C)=[O:45])=[O:38])([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C>[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH2:13][C:14]([N:42]([CH2:41][CH2:40][NH:39][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:43][C:44]([O:46][CH3:47])=[O:45])=[O:16])[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 10868DicyclohexylcarbodiimideHCID 4319362Ethyl N-{2-[(tert-butoxycarbonyl)amino]ethyl}glycinateHCID 22987109(7-methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid

生成物 1

HCID 22987110Methyl N-((7-Methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetyl)-N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate収率 41%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a precooled (0° C.) solution of (7-methyl-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid (0.995 g, 4.60 mmol) and DhbtOH (0.744 g, 4.60 mmol) in DMF (25 mL)was added DCC (1.04 g, 5.00 mmol) and the mixture was stirred for 40 min at 0° before addition of ethyl N-(2-(tert-butyloxycarbonyl)aminoethyl)glycinate (1.10 g, 5.0 mmol). This mixture was stirred at rt overnight, evaporated in vacuo, redissolved in ethyl acetate (75 mL) and washed with 5% aqueous NaHCO3 (3×25 mL) and with brine (2×25 mL). The organic phase was dried over MgSO4, filtered and evaporated in vacuo. The crude product purified on silica using dichloromethane/methanol (90:10 v/v) as the eluent. Fractions containing the product were pooled and evaporated in vacuo to yield the desired product (790 mg, 41%) (mp 98-100° C.). 1H NMR (DMSO-d6; this compound exist as two rotamers; chemical shifts for the minor rotamer is given in brackets): δ 12.05 (s br, 1H), 7.91 (7.96) (d, 8.0 Hz, 1H), 7.74 (7.71) (s, 1H), 7.10 (d, 8.0 Hz, 1H), 6.90 (6.99) (m, 1H), 4.05 (4.36) (s, 2H), 4.09 (q, J=5.2 Hz, 3H), 3.63 (s, 3H), 3.47 (m, 2H), 3.17 (s, 2H), 3.16 (s, 3H), 1.36 (1.35) (s, 9H). 13C NMR (DMSO-d6): δ 170.44 (170.66), 170.11, 162.65 (162.73), 159.22, 155.83 (155.71), 148.99, 136.43 (136.77), 136.04 (136.17), 128.61 (128.29), 118.21, 112.00 (112.07), 78.04, 51.81 (52.20), 47.63 (48.20), 38.59 (38.45), 33.42 (33.75), 28.27, 24.22. FAB+ HRMS: 433.2086, calc. C21H29N4O6 433.2087.

後処理

  1. customevaporated in vacuo
  2. dissolutionredissolved in ethyl acetate (75 mL)
  3. washwashed with 5% aqueous NaHCO3 (3×25 mL) and with brine (2×25 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product purified on silica
  8. additionFractions containing the product
  9. customevaporated in vacuo

出典と根拠

ORDレコード
ord-60efcd5a04b2465d9fca89f753c34acf
出典データセット
uspto-grants-2003_10
特許番号
US06632919B1

反応ノート

読み込み中…