4-Methylmorpholine → 1-[trans-4-(n-Tert-butoxycarbonylglycylamino)-n-tert-butoxycarbonyl-l-prolyl]-4-(3,5-dichlorophenoxy)piperidine

HRID 2185481노트

반응식

HRID 2185481 반응식
CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]([NH:31][C@H:32]1[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:34]([C:44](O)=[O:45])[CH2:33]1)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].[Cl:47][C:48]1[CH:49]=[C:50]([CH:58]=[C:59]([Cl:61])[CH:60]=1)[O:51][CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.ON1C2C=CC=CC=2N=N1>O1CCCC1.CN(C)C=O>[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]([NH:31][C@H:32]1[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:38])[C@H:34]([C:44]([N:55]2[CH2:56][CH2:57][CH:52]([O:51][C:50]3[CH:58]=[C:59]([Cl:61])[CH:60]=[C:48]([Cl:47])[CH:49]=3)[CH2:53][CH2:54]2)=[O:45])[CH2:33]1)=[O:30])=[O:26])([CH3:21])([CH3:22])[CH3:23]

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-prolineHCID 224584124-(3,5-Dichlorophenoxy)piperidine

생성물 1

HCID 701730401-[trans-4-(n-Tert-butoxycarbonylglycylamino)-n-tert-butoxycarbonyl-l-prolyl]-4-(3,5-dichlorophenoxy)piperidine수율 105.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

N-Methylmorpholine (120 μL) and ]-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (188 mg) were added to a solution of trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 400 mg), 4-(3,5-dichlorophenoxy)piperidine (518 mg), and 1-hydroxybenzotriazole (140 mg) in tetrahydrofuran (12 mL) and N,N-dimethylformamide (4 mL) at room temperature. After stirring at room temperature for 12 hr, the reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated sodium hydrogen carbonate and brine. After drying over anhydrous sodium sulfate, the organic layer was evaporated in vacuo. The residue was washed with hexane to give the titled compound (671 mg) as a white solid: 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.46 (s, 9H), 1.70-2.00 (m, 4H), 2.14-2.29 (m, 2H), 3.35-3.82 (m, 8H), 4.51-4.60 (m, 2H), 4.64 (br t, 0.5H), 4.78 (m, 0.5H), 5.11 (br s, 1H), 6.40 (m, 1H), 6.77-6.80 (m, 2H), and 6.96-6.98 (m, 1H); IR (KBr) 3311, 2978, 1701, 1655, 1570, 1441, 1255, 1163, 1049 cm−1; mass spectrum (FAB+) m/e 615 (M).

후처리

  1. customthe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. washThe organic layer was washed with saturated sodium hydrogen carbonate and brine
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. customthe organic layer was evaporated in vacuo
  5. washThe residue was washed with hexane

출처 및 근거

ORD 기록
ord-bb4820c8789047b185e83fa327df6c60
출처 데이터셋
uspto-grants-2002_06
특허 번호
US06399629B1

반응 노트

불러오는 중…