Diisopropylethylamine → 3-methoxy-4-[9-(2-methoxy-ethyl)-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 2111337

Reaction equation

HRID 2111337 reaction equation
[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]=[CH:15][C:16]2[N:22]([CH3:23])[C:21](=[O:24])[CH2:20][CH2:19][N:18]([CH2:25][CH2:26][O:27][CH3:28])[C:17]=2[N:29]=1)[C:6]([OH:8])=O.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)C(C)C)C.[NH2:63][CH:64]1[CH2:69][CH2:68][N:67]([CH3:70])[CH2:66][CH2:65]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[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]=[CH:15][C:16]2[N:22]([CH3:23])[C:21](=[O:24])[CH2:20][CH2:19][N:18]([CH2:25][CH2:26][O:27][CH3:28])[C:17]=2[N:29]=1)[C:6]([NH:63][CH:64]1[CH2:69][CH2:68][N:67]([CH3:70])[CH2:66][CH2:65]1)=[O:8]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 687404513-methoxy-4-[9-(2-methoxy-ethyl)-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-benzoic acidHCID 178484293HCID 178484293, compound

Product 1

HCID 576350443-methoxy-4-[9-(2-methoxy-ethyl)-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-N-(1-methyl-piperidin-4-yl)-benzamideYield 72.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 0.11 g (0.00027 mole) of 3-methoxy-4-[9-(2-methoxy-ethyl)-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-benzoic acid (I-40a), 0.115 g (0.0003 mole) of 1-[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.166 mL (0.00096 mole) of ethyldiisopropyl amine and 2.0 mL of dimethylformamide was stirred for 5 minutes and then 0.047 g (0.00041 mole) of 4-amino-1-methyl-piperidine was added. The mixture was stirred for 3 hours, then diluted with 10 mL of water plus 2 mL of saturated sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with an acetonitrile-water gradient (20:80-100:0) to give 0.098 g of 3-methoxy-4-[9-(2-methoxy-ethyl)-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-N-(1-methyl-piperidin-4-yl)-benzamide (I-40) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-3586ed85d1394ffda2e53a3367b24ad0
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Linked notes

Loading…