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 2200301ノート

反応式

HRID 2200301 の反応式
[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

参加物

8

反応物 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

生成物 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 dihydrochloride収率 110.8%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒2 回HCID 6228Dimethylformamide溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-0c226f8e31774607a6e6eaef2e88c038
出典データセット
uspto-grants-2016_06
特許番号
US09359340B2

反応ノート

読み込み中…