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Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}propanediamide

HRID 657406
ノート
印刷プレビュー

反応式

HRID 657406 の反応式
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:27][CH3:28])=[C:10]([CH2:19][NH:20][C:21](=[O:26])[CH2:22][C:23](O)=[O:24])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[NH2:29][CH2:30][C:31]1[CH:32]=[C:33]([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][CH:44]3[CH2:49][CH2:48][N:47](C(OC(C)(C)C)=O)[CH2:46][CH2:45]3)[CH:38]=2)[CH:34]=[CH:35][CH:36]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:27][CH3:28])=[C:10]([CH2:19][NH:20][C:21](=[O:26])[CH2:22][C:23]([NH:29][CH2:30][C:31]3[CH:32]=[C:33]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][CH:44]5[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]5)[CH:38]=4)[CH:34]=[CH:35][CH:36]=3)=[O:24])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57813360tert-Butyl 4-{[3'-(aminomethyl)biphenyl-3-yl]methyl}piperidine-1-carboxylateHCID 578198663-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-3-oxopropanoic acid

生成物 1

HCID 57819902
N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}propanediamide
収率 25.24%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To the solution of 3-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-3-oxopropanoic acid (0.0779 g, 0.200 mmol) in DCM (1 mL) was added 1,1-dimethylethyl 4-{[3′-(aminomethyl)-3-biphenylyl]methyl}-1-piperidinecarboxylate (0.0837 g, 0.220 mmol), HBTU (0.0910 g, 0.240 mmol), TEA (0.0563 mL, 0.400 mmol) and was stirred at room temperature for 16 hours. The reaction mixture was concentrated on Glas-Col evaporator, purified by Gilson HPLC and concentrated with Biotachi evaporator. The crude product was dissolved in DCM (0.6 mL) and TFA (0.2 mL) was added. The resultant mixture was left at room temperature for 1 hour before being concentrated on Glas-Col evaporator, purified by Gilson HPLC (with 0.1% TFA) and basified with amine cartridge to afford the title compound 0.0329 g (25.24%). LC-MS m/z 652 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.38 (t, J=7.65 Hz, 3H) 1.49 (t, J=7.28 Hz, 5H) 1.72-1.85 (m, 2H) 1.87-2.02 (m, 5H) 2.69 (d, J=6.78 Hz, 2H) 2.94 (td, J=12.80, 2.26 Hz, 2H) 3.05 (q, J=7.53 Hz, 2H) 3.37 (d, J=12.55 Hz, 2H) 3.59 (td, J=11.48, 2.13 Hz, 2H) 3.92 (dt, J=1.80, 3.51 Hz, 2H) 4.19-4.30 (m, 1H) 4.42-4.50 (m, 4H) 4.52 (s, 2H) 7.19 (d, J=7.53 Hz, 1H) 7.27-7.32 (m, 1H) 7.37 (td, J=7.59, 3.14 Hz, 2H) 7.44-7.52 (m, 3H) 7.57 (s, 1H) 8.24 (s, 1H).

後処理

  1. concentrationThe reaction mixture was concentrated on Glas-Col evaporator
  2. custompurified by Gilson HPLC
  3. concentrationconcentrated with Biotachi evaporator
  4. dissolutionThe crude product was dissolved in DCM (0.6 mL)
  5. additionTFA (0.2 mL) was added
  6. waitThe resultant mixture was left at room temperature for 1 hour
  7. concentrationbefore being concentrated on Glas-Col evaporator
  8. custompurified by Gilson HPLC (with 0.1% TFA)

出典と根拠

ORDレコード
ord-1eacf881af10472db33a70954bff42a7
出典データセット
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08071588B2

反応ノート

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