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Cesium carbonate → HCID 58014988, compound

HRID 1676772
Notes
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Reaction equation

HRID 1676772 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[C:25]([F:32])[C:24]=1[F:33].[C:34](=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:34][O:28][C:27](=[O:29])[C:26]1[CH:30]=[CH:31][C:23]([NH:22][C:2]2[N:3]=[CH:4][C:5]3[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)[C:6]=3[N:21]=2)=[C:24]([F:33])[C:25]=1[F:32]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27627754-Amino-2,3-difluorobenzoic acidHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Product 1

HCID 58014988HCID 58014988, compoundYield 76.6%

Reagents, catalysts & solvents 2

HCID 167845
palladium(II) acetate
Catalyst
HCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 0.4997 g (1.578 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20), 0.3539 g (1.891 mmole) of 4-amino-2,3-difluorobenzoic acid, and 25 mL of dioxane, was added 1.028 g (3.152 mmole) of cesium carbonate and 0.0367 g (0.163 mmole) of palladium acetate. The mixture was deoxygenated with argon, 0.2044 g (0.318 mmole) of 1,1′-[1,1′-binaphthalene]-2,2′-diylbis[1,1-diphenyl phosphine was added and the reaction mixture was heated at 100 degrees for 4 hrs. The cooled mixture was concentrated under reduced pressure, dissolved in ethyl acetate, made slightly acidic by the addition of 1M hydrochloric acid, washed with water, brine, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 95:5-80:20) gave 0.565 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2,3-difluoro-benzoic acid methyl ester (I-242) as off-white solid.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated at 100 degrees for 4 hrs
  3. concentrationThe cooled mixture was concentrated under reduced pressure
  4. dissolutiondissolved in ethyl acetate
  5. additionmade slightly acidic by the addition of 1M hydrochloric acid
  6. washwashed with water, brine
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica gel chromatography
  10. washeluting with dichloromethane-methanol (gradient, 95:5-80:20)

Sources & evidence

ORD record
ord-0e894640bd864cce8b37219f0298ed20
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08003785B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes