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

HRID 2111352Notes

Reaction equation

HRID 2111352 reaction equation
[CH:1]([N:4]1[CH2:10][CH2:9][C:8](=[O:11])[N:7]([CH3:12])[C:6]2[CH:13]=[N:14][C:15]([NH:17][C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][C:19]=3[O:27][CH3:28])=[N:16][C:5]1=2)([CH3:3])[CH3:2].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.[NH2:62][CH:63]1[CH2:68][CH2:67][N:66]([CH3:69])[CH2:65][CH2:64]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH:1]([N:4]1[CH2:10][CH2:9][C:8](=[O:11])[N:7]([CH3:12])[C:6]2[CH:13]=[N:14][C:15]([NH:17][C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH:62][CH:63]4[CH2:68][CH2:67][N:66]([CH3:69])[CH2:65][CH2:64]4)=[O:23])=[CH:20][C:19]=3[O:27][CH3:28])=[N:16][C:5]1=2)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 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 acidHCID 178484293HCID 178484293, compound

Product 1

HCID 250154664-(9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamideYield 66.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 0.077 g (0.0002 mole) of 4-(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 (I-43a), 0.091 g (0.00024 mole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.052 mL (0.0003 mole) of ethyldiisopropyl amine and 1.0 mL of dimethylformamide was stirred for 5 minutes and then 0.034 g (0.0003 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 0.064 g of 4-(9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-43) 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-78f5e113109c4975b9d3eced6762ecb7
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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