Diisopropylethylamine → HCID 57635020, compound

HRID 2111298Notes

Reaction equation

HRID 2111298 reaction equation
[CH:1]1([N:6]2[CH2:12][CH:11]([CH2:13][CH2:14][CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.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.[NH2:67][CH:68]1[CH2:73][CH2:72][N:71]([CH3:74])[CH2:70][CH2:69]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH:1]1([N:6]2[CH2:12][CH:11]([CH2:13][CH2:14][CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([NH:67][CH:68]5[CH2:73][CH2:72][N:71]([CH3:74])[CH2:70][CH2:69]5)=[O:28])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 57635009HCID 57635009, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 57635020HCID 57635020, compoundYield 76.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 0.200 g (0.00044 mole) of (rac)-4-(9-cyclopentyl-5-methyl-7-propyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl amino)-3-methoxy-benzoic acid (I-16), 0.200 g (0.00053 mole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.230 mL (0.0013 mole) of ethyldiisopropyl amine and 2 mL of dimethylformamide was stirred for 5 minutes and then 0.075 g (0.00066 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 0.186 g of (rac)-4-(9-cyclopentyl-5-methyl-7-propyl-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-17) 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-2b6f0dcb07ef431d898a8120b20b3f8d
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

Loading…