Triethylamine → tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1-phenylcyclopropyl)methyl]amino}propyl]pyrrolidine-1-carboxylate

HRID 74748ノート

反応式

HRID 74748 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([O:19][CH3:20])[C@@H:14]([CH3:18])[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[C:52]1([C:58]2([CH2:61][NH2:62])[CH2:60][CH2:59]2)[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>ClCCl.CN(C)C=O>[CH3:20][O:19][C@@H:13]([C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@@H:14]([CH3:18])[C:15](=[O:17])[NH:62][CH2:61][C:58]1([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:60][CH2:59]1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 702871-PhenylcyclopropanemethanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11033491(2R,3R)-3-((2S)-1-(tert-Butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acid

生成物 1

HCID 86685733tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1-phenylcyclopropyl)methyl]amino}propyl]pyrrolidine-1-carboxylate収率 68%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

According to general procedure D, from #11 (2.15 g, 7.48 mmol, 1.1 eq.) in dichloromethane (20 mL, 0.3 M) and N,N-dimethylformamide (4 mL), 1-(1-phenylcyclopropyl)methanamine #@1 (1.001 g, 6.799 mmol, 1 eq.), HATU (3.10 g, 8.16 mmol, 1.2 eq.) and triethylamine (2.84 mL, 20.4 mmol, 3 eq.) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane), producing #57 (1.93 g, 68%) as a solid. HPLC (Protocol A at 45° C.): m/z 417.3 [M+H+], retention time=10.575 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers: δ 7.75-7.81 (m, 1H), 7.20-7.27 (m, 4H), 7.12-7.19 (m, 1H), 3.33-3.62 and 3.71-3.80 (br multiplets, total 4H), 3.28 (s, 3H), 2.97-3.17 (br m, 2H), 2.14-2.24 (m, 1H), 1.67-1.80 (br m, 2H), 1.45-1.65 (m, 2H), 1.41 (s, 9H), 1.00 (d, J=6.6 Hz, 3H), 0.67-0.93 (m, 4H).

後処理

  1. customwas purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-2c3c906b7aa648c38c7cac4f77c7eaef
出典データセット
uspto-grants-2014_09
特許番号
US08828401B2

反応ノート

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