Methylamine → HCID 58015157, compound

HRID 1676668Notes

Reaction equation

HRID 1676668 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[NH:9][C:8]3[CH:16]=[N:17][C:18]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=4)=[N:19][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.[CH3:37][N:38](C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C.CN>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[NH:9][C:8]3[CH:16]=[N:17][C:18]([NH:20][C:21]4[CH:22]=[CH:23][C:24]([C:25]([NH:38][CH3:37])=[O:27])=[CH:28][CH:29]=4)=[N:19][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 58015066HCID 58015066, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 58015157HCID 58015157, compoundYield 19%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 0.075 g (0.19 mmole) of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-benzoic acid (I-131) and 0.09 g (0.24 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 0.06 mL (0.37 mmole) of diisopropylethylamine. The mixture was stirred for 30 minutes and then 0.14 mL (0.28 mmole) of 2M methylamine in tetrahydrofuran was added. The mixture was stirred at room temperature for 18 hours. The mixture was diluted with ethyl acetate and water and 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 ethyl acetate to give 0.015 g of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-methyl-benzamide (I-133).

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  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 ethyl acetate

Sources & evidence

ORD record
ord-fd223aea261b466196f11c8d2d0000ad
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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