Hydrochloric Acid → 2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(2,2,2-trifluoroethylamino)propan-1-one dihydrochloride

HRID 2200301노트

반응식

HRID 2200301 반응식
[ClH:1].Cl.[CH3:3][C@H:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[C@H:6]([OH:19])[CH2:5]1.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([CH2:31][NH:32][CH2:33][C:34]([F:37])([F:36])[F:35])[C:28]([O-])=[O:29])=[CH:23][CH:22]=1.[K+].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.CCOCC>[ClH:20].[ClH:1].[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([CH:27]([CH2:31][NH:32][CH2:33][C:34]([F:35])([F:36])[F:37])[C:28]([N:16]2[CH2:15][CH2:14][N:13]([C:11]3[C:12]4[C@H:4]([CH3:3])[CH2:5][C@@H:6]([OH:19])[C:7]=4[N:8]=[CH:9][N:10]=3)[CH2:18][CH2:17]2)=[O:29])=[CH:25][CH:26]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66617976Potassium 2-(4-chlorophenyl)-3-(2,2,2-trifluoroethylamino)propanoateHCID 66618034(5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride

생성물 1

HCID 866187412-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(2,2,2-trifluoroethylamino)propan-1-one dihydrochloride수율 110.8%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회HCID 6228Dimethylformamide용매

실험 절차

A solution of (5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (30 mg, 98 umol) and potassium 2-(4-chlorophenyl)-3-(2,2,2-trifluoroethylamino)propanoate (31.2 mg, 98 umol) in DMF (1.0 mL) was treated with DIEA (36 uL, 205 umol) and HBTU (41 mg, 107 umol), respectively, at room temperature. The mixture was allowed to stir for 18 hours to completion, and the solution was partitioned between ethyl acetate and water. The aqueous portion was extracted twice, and the organics were combined. The organic portion was washed with water (3×), then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel eluted with 9:1 ethyl acetate:MeOH) to afford the pure free-base as a colorless oil. This material was dissolved in ether (1.0 mL), then treated with excess 2.0M HCl in ether. The suspension was concentrated in vacuo to afford the pure 2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(2,2,2-trifluoroethylamino)propan-1-one dihydrochloride (31 mg, 99%) as a white solid. LCMS (APCI+) m/z 498.2 [M+H]+.

후처리

  1. customat room temperature
  2. customthe solution was partitioned between ethyl acetate and water
  3. extractionThe aqueous portion was extracted twice
  4. washThe organic portion was washed with water (3×)
  5. custombrine, separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography (silica gel eluted with 9:1 ethyl acetate:MeOH)
  10. customto afford the pure free-base as a colorless oil
  11. concentrationThe suspension was concentrated in vacuo

출처 및 근거

ORD 기록
ord-0c226f8e31774607a6e6eaef2e88c038
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359340B2

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