1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-tert-butoxycarbonyl L-prolyl L-prolyl O-allyl L-seryl L-valyl L-valine methyl ester

HRID 2370896ノート

反応式

HRID 2370896 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:22][CH2:21][CH2:20][C@H:9]1[C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14](O)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][O:24][C:25](=[O:47])[C@H:26]([CH:44]([CH3:46])[CH3:45])[NH:27][C:28](=[O:43])[C@H:29]([CH:40]([CH3:42])[CH3:41])[NH:30][C:31](=[O:39])[C@H:32]([CH2:34][O:35][CH2:36][CH:37]=[CH2:38])[NH2:33].C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:23][O:24][C:25](=[O:47])[C@H:26]([CH:44]([CH3:46])[CH3:45])[NH:27][C:28](=[O:43])[C@H:29]([CH:40]([CH3:42])[CH3:41])[NH:30][C:31](=[O:39])[C@H:32]([CH2:34][O:35][CH2:36][CH:37]=[CH2:38])[NH:33][C:14](=[O:15])[C@@H:13]1[CH2:17][CH2:18][CH2:19][N:12]1[C:10](=[O:11])[C@@H:9]1[CH2:20][CH2:21][CH2:22][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7]

参加物

6

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11864387Boc-Pro-Pro-OHHCID 86671349O-allyl L-seryl L-valyl L-valine methyl ester

生成物 1

HCID 86671350N-tert-butoxycarbonyl L-prolyl L-prolyl O-allyl L-seryl L-valyl L-valine methyl ester収率 93%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

N-tert-butoxycarbonyl L-prolyl L-proline 2 (3.80 g, 12.2 mmol) and O-allyl L-seryl L-valyl L-valine methyl ester 9 (4.35 g, 12.2 mmol) were dissolved in DMF (25 mL) and the solution cooled to 0° C. HOBt hydrate (1.87 g, 12.2 mmol) was added under stirring. EDC hydrochloride (2.57 g, 13.4 mmol) was added to the reaction mixture in small portions. The reaction mixture was stirred overnight and the solvent evaporated. The residue was taken up in EtOAc (50 mL) and washed with 2M HCl (3×25 mL), 7.5% (w/w) K2CO3 (3×25 mL) and saturated brine (20 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (7.34 g, 93%); δH (300 MHz; d6-DMSO) 8.10 (1H, d, J 8, NH(Valx)), 7.98 (1H, d, J 8, NH(Ser(All))), 7.60 (1H, d, J 9, NH(Valy), rotomer 1), 7.59 (1H, d, J 9, NH(Valy), rotomer 2), 5.83 (1H, ddt, J 5, 11 and 17, CH═CH2), 5.24 (1H, ddt, J 1, 3 and 17, CH═CHH), 5.14-5.09 (1H, m, CH═CHH), 4.46-4.37 (3H, m, CαH(Pro1)/CαH(Pro2)/CαH(Ser(All))), 4.32 (1H, dd, J 7 and 9, CαH(Valy)), 4.15-4.10 (1H, m, CαH(Valx)), 3.93 (2H, m, J 1 and 5, CH2CH═CH2), 3.67-3.50 and 3.36-3.24 (6H, m, CδH2(Pro1)/CδH2(Pro2)/CH2(Ser(All))), 3.61 (3H, s, OCH3), 2.26-1.71 (10H, m, CH2(Pro)/CH(CH3)2), 1.37 (9H, s, (CH3)3, rotomer 1), 1.30 (9H, s, (CH3)3, rotomer 2), 0.89-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.6, 171.5, 171.3, 171.1, 170.9, 170.4, 169.1, 169.1, 153.3, 152.9, 134.8, 116.5, 78.3, 78.1, 71.1, 69.3, 59.1, 57.4, 57.2, 56.9, 52.9, 51.4, 46.5, 46.4, 46.3, 46.3, 30.9, 30.6, 29.6, 29.5, 29.4, 28.7, 28.5, 28.1, 27.9, 24.4, 24.3, 23.6, 23.0; m/z (ESI) 674.3737 ([M+Na]+; C32H53N5O9Na requires 674.3741)

後処理

  1. stirringThe reaction mixture was stirred overnight
  2. customthe solvent evaporated
  3. washwashed with 2M HCl (3×25 mL), 7.5% (w/w) K2CO3 (3×25 mL) and saturated brine (20 mL)
  4. dry with materialThe solution was dried with anhydrous MgSO4
  5. customthe solvent evaporated

出典と根拠

ORDレコード
ord-7c70e96769bd4e24a4d68fa802a73c6b
出典データセット
uspto-grants-2014_04
特許番号
US08710008B2

反応ノート

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