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 2370896Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 0 °C

Procedure

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)

Workup

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

Sources & evidence

ORD record: ord-7c70e96769bd4e24a4d68fa802a73c6b
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710008B2

Reaction notes

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