Trifluoroacetic acid → N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)-4-((R)-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide

HRID 81000

반응식

HRID 81000 반응식
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:31][CH2:32][N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])[C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24](OC(C)(C)C)=O)[CH2:20][CH2:19]2)=[O:17])=[CH:11][CH:10]=1.C(N(CC)C(C)C)(C)C.ClC1[C:49]2[C@H:56]([CH3:57])[CH2:55][CH2:54][C:50]=2[N:51]=[CH:52][N:53]=1>C(Cl)Cl.O>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:31][CH2:32][N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])[C:16]([N:18]2[CH2:19][CH2:20][N:21]([C:24]3[C:49]4[C@H:56]([CH3:57])[CH2:55][CH2:54][C:50]=4[N:51]=[CH:52][N:53]=3)[CH2:22][CH2:23]2)=[O:17])=[CH:11][CH:10]=1

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineHCID 67134222tert-butyl 4-(N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)carbamoyl)piperazine-1-carboxylate

생성물 1

HCID 25171406N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)-4-((R)-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide수율 12.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

Trifluoroacetic acid (1 mL) was added to a solution of tert-butyl 4-(N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)carbamoyl)piperazine-1-carboxylate (311 mg, 0.7 mmol) in DCM (5 mL). The mixture was stirred at room temperature for 3 hours, and then concentrated in vacuo. The residue was dissolved in n-butanol (2 mL). N,N-Diisopropylethylamine (0.5 mL, 3.6 mmol) was added followed by (R)-4-chloro-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidine (113 mg, 0.84 mmol). The reaction mixture was heated at 80° C. for 16 hours. The mixture was then diluted with H2O, and extracted with DCM (2×20 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by preparative HPLC to give N-(4-chlorophenyl)-N-(2-(diethylamino)ethyl)-4-((R)-6,7-dihydro-5-methyl-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxamide (39.9 mg, 12%). MS (APCI+) [M+H]+ 471.3. 1H NMR (CDCl3, 400 MHz) δ□: 8.49 (s, 1H), 7.40-7.35 (m, 2H), 7.17-7.13 (m, 2H), 4.06-3.95 (m, 4H), 3.77-3.70 (m, 2H), 3.51-3.44 (m, 1H), 3.39-3.02 (m, 11H), 2.42-2.32 (m, 1H), 1.88-1.82 (m, 1H), 1.33 (t, J=7.2 Hz, 6H), 1.15 (d, J=6.8 Hz, 3H).

후처리

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in n-butanol (2 mL)
  3. temperatureThe reaction mixture was heated at 80° C. for 16 hours
  4. extractionextracted with DCM (2×20 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-3523bbb3388b46fea880b74a2d88a48d
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846683B2

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