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Hydrochloric Acid → [1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3h-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1h-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 79999
ノート
印刷プレビュー

反応式

HRID 79999 の反応式
C([O:5][C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:34]=[CH:33][C:32]5[C:27](=[CH:28][CH:29]=[C:30]([C:35]6[NH:36][C:37]([CH:40]7[CH2:46][C:43]8([CH2:45][CH2:44]8)[CH2:42][N:41]7[C:47](=[O:57])[CH:48]([NH:52]C(OC)=O)[CH:49]([CH3:51])[CH3:50])=[N:38][CH:39]=6)[CH:31]=5)[CH:26]=4)=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH:12]2[CH2:58][CH:9]1[CH2:10][CH2:11]2)=O)(C)(C)C.Cl.CN1C[CH2:65][O:64][CH2:63]C1.[CH3:67][O:68][C:69]([NH:71][CH:72]([CH2:76][CH3:77])C(O)=O)=[O:70].CN(C([O:85]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.CN(C=O)C>[CH3:63][O:64][C:65](=[O:85])[NH:52][CH:48]([C:47]([N:41]1[CH:40]([C:37]2[NH:36][C:35]([C:30]3[CH:29]=[CH:28][C:27]4[C:32](=[CH:33][CH:34]=[C:25]([C:22]5[CH:21]=[CH:20][C:19]([C:16]6[NH:15][C:14]([CH:13]7[CH:12]8[CH2:58][CH:9]([CH2:10][CH2:11]8)[N:8]7[C:6](=[O:5])[CH:72]([NH:71][C:69]([O:68][CH3:67])=[O:70])[CH2:76][CH3:77])=[N:18][CH:17]=6)=[CH:24][CH:23]=5)[CH:26]=4)[CH:31]=3)=[CH:39][N:38]=2)[CH2:46][C:43]2([CH2:44][CH2:45]2)[CH2:42]1)=[O:57])[CH:49]([CH3:50])[CH3:51]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 434699742-Methoxycarbonylamino-butyric acidHCID 666207943-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl]-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

生成物 1

HCID 66620756[1-(6-{5-[6-(4-{2-[2-(2-Methoxycarbonylamino-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3h-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1h-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester収率 80.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

To 3-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (60 mg, 0.077 mmol) in dioxanes (2 mL) and MeOH (0.5 mL) was added 4N HCl in dioxanes (160 μL). The suspension was stirred for 2 h then concentrated to afford the HCL salt of the crude amine. To the crude amine in DMF (1 mL) was added N-methylmorpholine (34 μL, 0.31 mmol), 2-methoxycarbonylamino-butyric acid (19 mg, 0.11 mmol) and HATU (35 mg, 0.09 mmol). After stirring for overnight the reaction was quenched with formic acid then purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier) to afford the title product (51 mg, 0.062 mmol, 80% yield). LCMS-ESI+: calc'd for C47H55N8O6: 827.4 (M+H+). Found: 827.4 (M+H+).

後処理

  1. concentrationthen concentrated
  2. customto afford the HCL salt of the crude amine
  3. stirringAfter stirring for overnight the reaction
  4. customwas quenched with formic acid
  5. customthen purified by reverse phase preparative HPLC (5-45% MeCN—H2O; 0.1% formic acid modifier)

出典と根拠

ORDレコード
ord-557ac123ec6e4cd69a721a0a2e337988
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08841278B2

反応ノート

読み込み中…

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