Diisopropylethylamine → N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl ester

HRID 2370897노트

반응식

HRID 2370897 반응식
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:18])[CH3:17])[NH2:15].[C:24]([O:28][C:29]([NH:31][C@H:32]([C:42](O)=[O:43])[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:17])[CH3:18])[NH:15][C:42](=[O:43])[C@H:32]([CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[NH:31][C:29]([O:28][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:30]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86671346L-valyl L-valine methyl ester trifluoroacetate

생성물 1

HCID 86671351N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl ester수율 95%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

실험 절차

L-valyl L-valine methyl ester trifluoroacetate 6 (11.62 g, 33.75 mmol) was dissolved in 60 mL DMF. N-tert-butoxycarbonyl O-benzyl L-serine 14 (9.97 g, 33.8 mmol) was added together with 10 mL DMF. The solution was cooled to 0° C. (icebath) before N,N-diisopropylethyl amine (4.36 g, 33.7 mmol), HOBt hydrate (5.17 g, 33.8 mmol) and EDC hydrochloride (7.12 g, 37.1 mmol) were added together with an additional 30 mL DMF. The reaction mixture was stirred overnight and the solvent evaporated. The residue was taken up in 200 mL EtOAc and washed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a white solid (16.22 g, 95%); δH (300 MHz; d6-DMSO) 8.20 (1H, d, J 8, NH(Valx)), 7.65 (1H, d, J 9, NH(Valy)), 7.35-7.23 (5H, m, Ph), 7.08 (1H, d, J 8, NH(Ser(Bn)), 4.46 (2H, s, CH2Ph), 4.35 (1H, dd, J 7 and 9, CαH(Valy)), 4.25 (1H, m, CαH(Ser(Bn))), 4.12 (1H, dd, J 6 and 8, CαH(Valx)), 3.63-3.54 (2H, m, CH2), 3.60 (3H, s, OCH3), 2.07-1.89 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.88-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.6, 171.0, 169.4, 155.1, 138.0, 128.0, 127.3, 127.3, 78.2, 71.9, 69.8, 57.4, 56.8, 54.5, 51.4, 31.1, 29.5, 28.0, 18.9, 18.7, 18.2, 17.7; m/z (ESI) 530.2824 ([M+Na]+; C26H41N3O7Na requires 530.2842)

후처리

  1. customthe solvent evaporated
  2. washwashed with 2M aqueous H2SO4 (3×80 mL), 7.5% (w/w) aqueous K2CO3 (3×80 mL) and saturated brine (80 mL)
  3. dry with materialThe solution was dried with anhydrous MgSO4
  4. customthe solvent evaporated

출처 및 근거

ORD 기록
ord-c8543a77007647dc9aec47fa7aa0063e
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08710008B2

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