Hydrochloric Acid → (3S,5S,8S)-3-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-8-tert-butyl-7,10-dioxo-5-(4-pyridin-2-ylbenzyl)-2,11-dioxa-6,9-diazadodec-1-yl (dimethylamino)acetate

HRID 1174413ノート

反応式

HRID 1174413 の反応式
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([C:58]([CH3:61])([CH3:60])[CH3:59])[C:14]([NH:16][C@@H:17]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C@@H:18]([O:47][CH2:48]SC)[CH2:19][C@@H:20]([NH:34][C:35](=[O:46])[C@H:36]([C:42]([CH3:45])([CH3:44])[CH3:43])[NH:37][C:38]([O:40][CH3:41])=[O:39])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:24][CH:23]=2)=[O:15])[C:9]1=[O:62])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:64][N:65]([CH3:70])[CH2:66][C:67]([OH:69])=[O:68].IN1C(=O)CCC1=O.Cl>O1CCOCC1>[CH3:64][N:65]([CH2:66][C:67]([O:69][CH2:48][O:47][C@H:18]([C@@H:17]([NH:16][C:14](=[O:15])[C@@H:13]([N:10]1[CH2:11][CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]1=[O:62])[C:58]([CH3:61])([CH3:60])[CH3:59])[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:19][C@H:20]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1)[NH:34][C:35](=[O:46])[C@H:36]([C:42]([CH3:45])([CH3:43])[CH3:44])[NH:37][C:38](=[O:39])[O:40][CH3:41])=[O:68])[CH3:70]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 75605N,N-Dimethylglycine hydrochlorideHCID 120273N-IodosuccinimideHCID 67407202N1-[(1S,3S,4S)-4-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-3-[(methylthio)methoxy]-5-phenyl-1-(4-pyridin-2-ylbenzyl)pentyl]-N2-(methoxycarbonyl)-3-methyl-L-valinamide

生成物 1

HCID 86646202(3S,5S,8S)-3-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-8-tert-butyl-7,10-dioxo-5-(4-pyridin-2-ylbenzyl)-2,11-dioxa-6,9-diazadodec-1-yl (dimethylamino)acetate

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

To a solution of the product from Example 195A (0.045 g, 0.052 mmol) in 1,2-dichloromethane (1.5 mL) were added molecular sieves (4 Å, 0.24 g), N,N-dimethylglycine hydrochloride (0.075 g, 0.537 mmol), followed by N-iodosuccinimide (0.013 g, 0.058 mmol), and the mixture was stirred at room temperature for 2 hours. The reaction was filtered through celite. The filtrate was diluted with ethyl acetate and was washed with a mixture of dilute NaHCO3 and Na2S2O3, dried over MgSO4, filtered and evaporated. The residue was dissolved in ether and 2 equivalents of 4 N HCl in dioxane were added. The crude product was purified by chromatography on silica gel eluting with a gradient starting with dichloromethane and ending with methanol to give the title compound as the bis hydrochloride salt (0.037 g, 77% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.87 (s, 9 H), 0.88 (s, 9 H), 1.60-1.73 (m, 2 H), 2.22 (s, 6 H), 2.29 (q, J=9.6 Hz, 1 H), 2.54-2.84 (m, 6 H), 2.93 (q, J=8.8 Hz, 1 H), 3.08-3.24 (m, 4 H), 3.53 (s, 3 H), 3.72-3.76 (m, 1 H), 3.87 (d, J=9.6 Hz, 1 H), 4.11-4.35 (m, 5 H), 5.26 (d, J=6.6 Hz, 1 H), 5.37 (d, J=6.6 Hz, 1 H), 6.78 (d, J=9.6 Hz, 1 H), 6.94-7.15 (m, 5 H), 7.22-7.40 (m, 8 H), 7.82-7.95 (m, 6 H), 8.63 (m, 1 H).

後処理

  1. filtrationThe reaction was filtered through celite
  2. additionThe filtrate was diluted with ethyl acetate
  3. washwas washed with a mixture of dilute NaHCO3 and Na2S2O3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in ether
  8. customThe crude product was purified by chromatography on silica gel eluting with a gradient

出典と根拠

ORDレコード
ord-316df44c94e94e2daf0e6cd75c6d0455
出典データセット
uspto-grants-2010_11
特許番号
US07834043B2

反応ノート

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