Cesium carbonate → HCID 58015047, 화합물

HRID 1676762노트

반응식

HRID 1676762 반응식
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[C:31]([F:32])=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[C:25]([F:33])[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[C:31]([F:32])=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[C:25]([F:33])[CH:24]=4)=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 201514774-Amino-2,5-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

생성물 1

HCID 58015047HCID 58015047, 화합물수율 40.7%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

To a mixture of 0.9503 g (3.0 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), 0.6252 g (3.611 mmole) of 4-amino-2,5-difluorobenzoic acid, and 48 mL of dioxane, was added 1.96 g (6.01 mmole) of cesium carbonate and 0.0682 g (0.304 mmole) of palladium acetate. The mixture was deoxygenated with argon, 0.386 g (0.621 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 3 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 0.5533 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)-2,5-difluoro-benzoic acid (I-232) as off-white solid.

후처리

  1. additionwas added
  2. temperaturethe reaction mixture was heated at 100 degrees for 3 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)

출처 및 근거

ORD 기록
ord-082adb8b8fde484693c320a356ad7d51
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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