N-(2-Aminoethyl)piperidine → 3-methoxy-4-[(2-methyl-3-oxo-6-propan-2-yl-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl)amino]-N-[2-(1-piperidyl)ethyl]benzamide

HRID 2234281ノート

反応式

HRID 2234281 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[NH:12][C:13]1[N:14]=[C:15]2[C:21](=[CH:22][N:23]=1)[N:20]([CH3:24])[C:19](=[O:25])[CH2:18][CH2:17][N:16]2[CH:26]([CH3:28])[CH3:27])[C:6](O)=[O:7].[NH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[NH:12][C:13]1[N:14]=[C:15]2[C:21](=[CH:22][N:23]=1)[N:20]([CH3:24])[C:19](=[O:25])[CH2:18][CH2:17][N:16]2[CH:26]([CH3:28])[CH3:27])[C:6]([NH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:7]

参加物

7

反応物 4

HCID 33944N-(2-Aminoethyl)piperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686813864-(9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

生成物 1

HCID 686824023-methoxy-4-[(2-methyl-3-oxo-6-propan-2-yl-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl)amino]-N-[2-(1-piperidyl)ethyl]benzamide

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of the hydrochloride salt of 3-methoxy-4-[(2-methyl-3-oxo-6-propan-2-yl-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl)amino]benzoic acid (Example 204; 127 mg, 0.33 mmol) and 1-(2-aminoethyl)piperidine (Aldrich, 54 uL, 0.38 mmol) and DIPEA (157 uL, 0.9 mmol) in anhydrous DMA (10 mL) at room temperature under nitrogen was added HATU (126 mg, 0.33 mmol) as a solid and the resulting solution stirred at room temperature overnight. The reaction mixture was loaded onto a SCX-3 column pre-wet with Methanol and the column washed with Methanol. The column was eluted with Ammonia in Methanol and product containing fractions evaporated. The resultant material was dissolved in dichloromethane and chromatographed with 2-5-10-20% methanol/dichloromethane followed by 7N ammonia/methanol. Evaporation of product containing fractions gave a yellow foam which was purified by reverse phase HPLC to yield the title compound as an off white gum (75 mg, 46%)

後処理

  1. washthe column washed with Methanol
  2. washThe column was eluted with Ammonia in Methanol and product
  3. additioncontaining fractions
  4. customevaporated
  5. dissolutionThe resultant material was dissolved in dichloromethane
  6. customchromatographed with 2-5-10-20% methanol/dichloromethane
  7. customEvaporation of product
  8. additioncontaining fractions
  9. customgave a yellow foam which
  10. customwas purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-191c9566175346e197d52d31eed43ff5
出典データセット
uspto-grants-2010_05
特許番号
US07709471B2

反応ノート

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