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Diisopropylethylamine → Benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-morpholin-4-ylquinolin-3-yl]carbamate

HRID 924442
ノート
印刷プレビュー

反応式

HRID 924442 の反応式
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:28]([OH:30])=O)=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][C:37]=1[N:38]1[CH2:43][C@H:42]([CH3:44])[C@@H:41]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[C@H:40]([NH:53][C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[CH2:39]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>[C:56]([O:55][C:54]([NH:53][C@H:40]1[C@H:41]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[C@@H:42]([CH3:44])[CH2:43][N:38]([C:37]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[NH:31][C:28]([C:13]2[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:39]1)=[O:60])([CH3:57])([CH3:58])[CH3:59]
参加物実験手順後処理出典と根拠反応ノート

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 59226553tert-butyl (3R,4R,5S)-1-(3-aminopyridin-4-yl)-4-(tert-butyldimethylsilyloxy)-5-methylpiperidin-3-ylcarbamateHCID 867268923-{[(Benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acid

生成物 1

HCID 86726893
Benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-morpholin-4-ylquinolin-3-yl]carbamate
収率 38.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acid (0.005 g, 0.01 mmol), tert-butyl ((3R,4R,5S)-1-(3-aminopyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (0.0064 g, 0.015 mmol), and HATU (0.012 g, 0.031 mmol) in DMF (0.2 mL) and DIPEA (0.0064 mL, 0.037 mmol) was stirred at room temperature for 2 h. The mixture was quenched with 5 mL of EtOAc and 3 mL of 1 M NaOH. The resulting layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were concentrated under reduced pressure, then purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.05% TFA, at a flow rate of 30 mL/min.) to afford the sub-title compound (0.0032 g, 30%). LCMS calc. for C44H60N7O7Si [M+H]+: m/z=826.4. found: 826.4.

後処理

  1. customThe mixture was quenched with 5 mL of EtOAc and 3 mL of 1 M NaOH
  2. customThe resulting layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. concentrationThe combined organic extracts were concentrated under reduced pressure
  5. custompurified by preparative HPLC (XBridge™ C18 column
  6. washeluting with a gradient of MeCN/water containing 0.05% TFA, at a flow rate of 30 mL/min.)

出典と根拠

ORDレコード
ord-4026de91408b4147af33aa972f110d24
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

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