4-Methylpiperazine-1-ethylamine → HCID 44548099, compound

HRID 1676592Notes

Reaction equation

HRID 1676592 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][NH2:42])[CH2:36][CH2:35]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:42][CH2:41][CH2:40][N:37]5[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]5)=[O:28])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 5

HCID 702844-Methylpiperazine-1-ethylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 178484293HCID 178484293, compound

Product 1

HCID 44548099HCID 44548099, compoundYield 16.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 0.100 g (0.22 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.039 g (0.33 mmole) of 2-(4-methyl-piperazin-1-yl)-ethylamine, 0.102 g (0.27 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.036 g (0.27 mmole) of 1-hydroxybenzotriazole, 0.195 mL (1.12 mmole) of diisopropylethyl amine and 2.0 mL of dimethylformamide was stirred for 18 hours. The mixture was diluted with 10 mL of water plus 2 mL of saturated aqueous sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 20:80-100:0) to give 0.021 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-[2-(4-methyl-piperazin-1-yl)-ethyl]-benzamide (I-47) as a white solid.

Workup

  1. extractionextracted 3 times with 10 mL of ethyl acetate
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by C18 reverse phase silica gel chromatography
  7. washeluting with acetonitrile-water (gradient, 20:80-100:0)

Sources & evidence

ORD record
ord-e34815439f7f4c2ead1c443eeac1f1c5
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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