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

HRID 1676700Notes

Reaction equation

HRID 1676700 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH2:16][CH2:17][CH3:18])[C:8]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][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)CC)(C)C.[NH2:68][CH:69]1[CH2:74][CH2:73][O:72][CH2:71][CH2:70]1>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH2:16][CH2:17][CH3:18])[C:8]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([NH:68][CH:69]5[CH2:74][CH2:73][O:72][CH2:71][CH2:70]5)=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 4192234-AminotetrahydropyranHCID 580150924-(9-cyclopentyl-5-propyl-7,7-difluoro-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 580151074-(9-cyclopentyl-7,7-difluoro-6-oxo-5-propyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(tetrahydro-pyran-4-yl)-benzamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 0.05 g, 0.11 mmole) of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-5-propyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-162), 0.06 g (0.16 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate and 2 mL of dimethylformamide was added 0.05 mL of 0.32 mmole) of diisopropylethylamine. After stirring at room temperature for 30 minutes 0.032 g (0.32 mmole) of 4-aminotetrahydropyran was added. The mixture was stirred at room temperature for 18 hours and then diluted with ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with water then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with hexanes-ethyl acetate (30:70) to give 0.046 g of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-5-propyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(tetrahydro-pyran-4-yl)-benzamide (I-167).

Workup

  1. additionwas added
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialbrine, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with hexanes-ethyl acetate (30:70)

Sources & evidence

ORD record
ord-bbab9092772c4a1bb879adb59141f376
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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