Diisopropylethylamine → N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert-butoxy-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 2282868ノート

反応式

HRID 2282868 の反応式
[CH3:1][O:2][C@@H:3]([C@@H:24]1[CH2:28][CH2:27][CH2:26][NH:25]1)[C@@H:4]([CH3:23])[C:5]([NH:7][C@H:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6].[CH:29]1[C:41]2[CH:40]([CH2:42][O:43][C:44]([NH:46][C:47]([CH3:72])([C:49]([NH:51][C@H:52]([C:56]([N:58]([C@@H:60]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:61]([O:66][CH3:67])[CH2:62][C:63](O)=[O:64])[CH3:59])=[O:57])[CH:53]([CH3:55])[CH3:54])=[O:50])[CH3:48])=[O:45])[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]=2[CH:32]=[CH:31][CH:30]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C.C(OCC)(=O)C>[CH:29]1[C:41]2[CH:40]([CH2:42][O:43][C:44]([NH:46][C:47]([CH3:72])([C:49]([NH:51][C@H:52]([C:56]([N:58]([C@@H:60]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:61]([O:66][CH3:67])[CH2:62][C:63]([N:25]3[CH2:26][CH2:27][CH2:28][C@H:24]3[C@H:3]([O:2][CH3:1])[C@@H:4]([CH3:23])[C:5]([NH:7][C@@H:8]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:6])=[O:64])[CH3:59])=[O:57])[CH:53]([CH3:55])[CH3:54])=[O:50])[CH3:48])=[O:45])[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]=2[CH:32]=[CH:31][CH:30]=1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86685741L-Valinamide, N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(1S,2S)-1-[(1R)-2-carboxy-1-methoxyethyl]-2-methylbutyl]-N-methyl-HCID 86685746tert-butyl N-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoyl}-L-phenylalaninate

生成物 1

HCID 86685745N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert-butoxy-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide収率 63.1%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirring solution of #121 (0.55 g, 1.0 mmol, 1.0 eq.) in 10 mL of dichloromethane and 1 mL of DMF, #32 (0.62 g, 1.0 mmol, 1.0 eq.) was added followed by HATU (0.42 g, 1.1 mmol, 1.1 eq.) and Hunig's base (0.72 mL, 4.1 mmol, 4.0 eq.). The reaction was allowed to stir at room temperature for approximately 21 hours. Reaction was reduced down, diluted with ethyl acetate, and then washed with 0.5 N HCl and brine. Organic layer was dried over sodium sulfate, filtered, and concentrated to a smaller volume before being concentrated down onto silica. Silica chromatography was then performed (Gradient: 0%-40% acetone in heptane) producing #122 (0.62 g, 62%) as a white solid. LC-MS (Protocol Q): m/z 982.3 [M+H+] retention time=2.44 minutes.

後処理

  1. customReaction
  2. washwashed with 0.5 N HCl and brine
  3. dry with materialOrganic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a smaller volume
  6. concentrationbefore being concentrated down onto silica

出典と根拠

ORDレコード
ord-ede1a782b4264492a8b9c48998e2dc45
出典データセット
uspto-grants-2015_09
特許番号
US09138486B2

反応ノート

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