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Diisopropylethylamine → Benzyl [2-[({4-[(3R,4S,5S)-3-[(tert-Butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate

HRID 924511
ノート
印刷プレビュー

反応式

HRID 924511 の反応式
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:29](O)=[O:30])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1[N:39]1[CH2:44][C@H:43]([CH3:45])[C@H:42]([N:46]2[CH:50]=[CH:49][N:48]=[N:47]2)[C@H:41]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:40]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>CN(C=O)C.C1COCC1.CO.O>[C:54]([O:53][C:52]([NH:51][C@H:41]1[C@@H:42]([N:46]2[CH:50]=[CH:49][N:48]=[N:47]2)[C@@H:43]([CH3:45])[CH2:44][N:39]([C:38]2[CH:37]=[CH:36][N:35]=[CH:34][C:33]=2[NH:32][C:29]([C:13]2[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:40]1)=[O:58])([CH3:57])([CH3:56])[CH3:55]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

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 867269043-{[(Benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acidHCID 86726946tert-Butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate

生成物 1

HCID 86726951
Benzyl [2-[({4-[(3R,4S,5S)-3-[(tert-Butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate
収率 49.1%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid (9.9 mg, 0.024 mmol), tert-butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate (8.0 mg, 0.021 mmol), and HATU (26 mg, 0.069 mmol), in DMF (0.23 mL) and THF (0.5 mL), DIPEA (0.014 mL, 0.083 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was diluted with MeOH and H2O, filtered and purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the sub-title compound as bright yellow powder (8.0 mg, 48%). LCMS calc. for C41H50N11O5 (M+H)+: m/z=776.4. Found: 776.3.

後処理

  1. filtrationfiltered
  2. custompurified by preparative LCMS (pH=10 method
  3. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

出典と根拠

ORDレコード
ord-a6487ebed5724c0d9845de0417c9bfbc
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09278950B2

反応ノート

読み込み中…

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