Diisopropylethylamine → (9R,11S, 14S,20E)-14-cyclohexyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-13-oxo-8-oxa-12,15-diazatetracyclo[20.3.1.12,6.19,12]octacosa-1(26),2(28),3,5,20,22,24-heptaene-11-carboxamide

HRID 1879268ノート

反応式

HRID 1879268 の反応式
[Cl-].[CH:2]1([S:5]([NH:8][C:9]([C@@:11]2([NH3+:16])[CH2:13][C@H:12]2[CH:14]=[CH2:15])=[O:10])(=[O:7])=[O:6])[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:41]1([C@@H:47]2[NH:71][CH2:70][CH2:69][CH2:68][CH2:67][CH:66]=[CH:65][C:64]3[CH:72]=[C:60]([CH:61]=[CH:62][CH:63]=3)[C:59]3=[CH:73][C:55](=[CH:56][CH:57]=[CH:58]3)[CH2:54][O:53][C@H:52]3[CH2:74][N:49]([C@H:50]([C:75](O)=[O:76])[CH2:51]3)[C:48]2=[O:78])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:41]1([C@@H:47]2[NH:71][CH2:70][CH2:69][CH2:68][CH2:67][CH:66]=[CH:65][C:64]3[CH:72]=[C:60]([CH:61]=[CH:62][CH:63]=3)[C:59]3=[CH:73][C:55](=[CH:56][CH:57]=[CH:58]3)[CH2:54][O:53][C@H:52]3[CH2:74][N:49]([C@H:50]([C:75]([NH:16][C@:11]4([C:9]([NH:8][S:5]([CH:2]5[CH2:4][CH2:3]5)(=[O:7])=[O:6])=[O:10])[CH2:13][C@H:12]4[CH:14]=[CH2:15])=[O:76])[CH2:51]3)[C:48]2=[O:78])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

参加物

6

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 58005172(9R,11S,14S,20E)-14-cyclohexyl-13-oxo-8-oxa-12,15-diazatetracyclo[20.3.1.12,6.19,12]octacosa-1(26),2(28),3,5,20,22,24-heptaene-11-carboxylic acidHCID 86637110[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]azanium chloride

生成物 1

HCID 86637111(9R,11S, 14S,20E)-14-cyclohexyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-13-oxo-8-oxa-12,15-diazatetracyclo[20.3.1.12,6.19,12]octacosa-1(26),2(28),3,5,20,22,24-heptaene-11-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

48 (1.2 eq.) and HATU (1.2 eq.) were added to a 0.12M solution of (9R,11S,14S,20E)-14-cyclohexyl-13-oxo-8-oxa-12,15-diazatetracyclo[20.3.1.12,6.19,12]octacosa-1(26),2(28),3,5,20,22,24-heptaene-11-carboxylic acid 111 in DMF containing DIPEA (4.0 eq.). The reaction mixture was stirred at RT overnight then it was concentrated to dryness and the residue was dissolved in DMSO and purified by RP-HPLC (stationary phase: column WATERSXBRIDGE 19×150 mm, 5 μm; mobile phase: MeCN/H2O buffered with 0.1% TFA from 50% to 90% of MeCN in 14 min., run time 18 min.). Fractions containing the pure compound were combined and freeze dried to afford compound 146 (TFA salt) as an off white solid (4.0% over 3 steps). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 10.73 (s, 1H), 8.83 (s, 1H), 8.80-8.68 (m, 1H), 8.58-8.42 (m, 1H), 7.92 (s, 2H), 7.68 (d, J 7.6, 1H), 7.62 (d, J 7.6, 1H), 7.51-7.40 (m, 2H), 7.29 (t, J 8.1, 2H), 6.58 (d, J 15.7, 1H), 6.49-6.37 (m, 1H), 5.68-5.54 (m, 1H), 5.27 (d, J 16.9, 1H), 5.16 (d, J 11.6, 1H), 4.74 (d, J 11.9, 1H), 4.60 (d, J 11.9, 1H), 4.50-4.33 (m, 3H), 4.19 (d, J 11.1, 1H), 3.86 (dd, J 11.1, 3.8, 1H), 3.18-2.91 (m, 3H), 2.60-2.46 (m, partially obscured by residual DMSO-d6, 1H), 2.43-2.24 (m, 2H), 2.19 (q, J 8.8, 1H), 2.09-1.97 (m, 1H), 1.92-1.65 (m, 9H), 1.64-1.52 (m, 1H), 1.38-1.02 (m, 11H). MS (ES) m/z 729 (M+H)+.

後処理

  1. concentrationit was concentrated to dryness
  2. dissolutionthe residue was dissolved in DMSO
  3. custompurified by RP-HPLC (stationary phase: column WATERSXBRIDGE 19×150 mm, 5 μm; mobile phase: MeCN/H2O buffered with 0.1% TFA from 50% to 90% of MeCN in 14 min., run time 18 min.)
  4. additionFractions containing the pure compound
  5. customfreeze dried

出典と根拠

ORDレコード
ord-9a0f03f80c034965930a9f809f8898e4
出典データセット
uspto-grants-2012_11
特許番号
US08314062B2

反応ノート

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