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Diisopropylethylamine → 4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-propyl-4-piperidyl)benzamide

HRID 2234308
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HRID 2234308 반응식
[CH:1]1([N:6]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]([CH3:18])[C:12]3[C:7]2=[N:8][C:9]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][C:21]=2[O:29][CH3:30])=[N:10][CH:11]=3)[CH2:5][CH2:4][CH2:3][CH2:2]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.[NH2:64][CH:65]1[CH2:70][CH2:69][N:68]([CH2:71][CH2:72][CH3:73])[CH2:67][CH2:66]1>CC(N(C)C)=O.CO>[CH:1]1([N:6]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]([CH3:18])[C:12]3[C:7]2=[N:8][C:9]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([NH:64][CH:65]4[CH2:70][CH2:69][N:68]([CH2:71][CH2:72][CH3:73])[CH2:67][CH2:66]4)=[O:25])=[CH:22][C:21]=2[O:29][CH3:30])=[N:10][CH:11]=3)[CH2:5][CH2:4][CH2:3][CH2:2]1
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참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 5417301-Propylpiperidin-4-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 426102404-(9-cyclopentyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

생성물 1

HCID 68683618
4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-propyl-4-piperidyl)benzamide
수율 65%

시약·촉매·용매 2

HCID 887Methanol용매HCID 31374Dimethylacetamide용매

실험 절차

4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-benzoic acid (Example 111; 231 mg, 0.56 mmol), DIPEA (0.3 mL, 1.68 mmol) and HATU (283 mg, 0.75 mmol) were stirred together in DMA (4 mL) at ambient temperature for 10 minutes. 4-amino-1-propylpiperidine (Fluorochem; 100 mg, 0.70 mmol) was added and the mixture stirred at room temperature for 4 hours. The reaction mixture was loaded onto an SCX-2 (10 g) column pre-wet with MeOH. The column was washed with MeOH (×2) and the product eluted with 2M NH3/MeOH. Product containing fractions were combined and evaporated and the residue purified by base modified reverse phase preparative HPLC. Product containing fractions were combined and evaporated to yield the title compound as a gum (194 mg, 65%).

후처리

  1. washThe column was washed with MeOH (×2)
  2. washthe product eluted with 2M NH3/MeOH
  3. additionProduct containing fractions
  4. customevaporated
  5. customthe residue purified by base modified reverse phase preparative HPLC
  6. additionProduct containing fractions
  7. customevaporated

출처 및 근거

ORD 기록
ord-512e18277659408da33fa8b903bce388
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07709471B2

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