Cyclopropylamine → 4-[(R)-[[4-[5-[(Cyclopropylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl ester

HRID 1697285노트

반응식

HRID 1697285 반응식
CO[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[C:15](Br)[N:14]=[C:13](Br)[C:12]2=[O:19])[CH:5]=1.[C:21]1([CH2:27][O:28][C:29]([N:31]2[CH2:36][CH2:35][CH:34]([C@@H:37]([NH2:44])[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:33][CH2:32]2)=[O:30])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH:45]1([NH2:48])[CH2:47][CH2:46]1.C1([Mg]Br)CCCC1.C([O-])=O.[NH4+]>C1COCC1.[Pd].C(O)C.C(N(CC)CC)C>[CH:45]1([NH:48][C:3]([C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:44][C@@H:37]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:34]4[CH2:33][CH2:32][N:31]([C:29]([O:28][CH2:27][C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=5)=[O:30])[CH2:36][CH2:35]4)[C:12]3=[O:19])[CH:5]=2)=[O:20])[CH2:47][CH2:46]1

참가 물질

10

반응물 5

HCID 69828CyclopropylamineHCID 2723923Ammonium formateHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 666897524-[(R)-aminophenylmethyl]-1-piperidinecarboxylic acid phenylmethyl esterHCID 178419650HCID 178419650, 화합물

생성물 1

HCID 666864344-[(R)-[[4-[5-[(Cyclopropylamino)carbonyl]-2-methylphenyl]-3,4-dihydro-3-oxopyrazinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl ester

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

반응 조건

온도
120 °C

실험 절차

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid methyl ester (Example 1b, 0.1 g) in anhydrous THF (2 mL) within a microwave vial was added triethylamine (100 μL) and 4-[(R)-aminophenylmethyl]-1-piperidinecarboxylic acid phenylmethyl ester (Example 101b, 98 mg). The reaction was heated within a microwave at 120° C. for 60 minutes before cooling to room temperature and adding cyclopropylamine (150 μL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise After stirring for 30 minutes, ethanol (2 mL) was added followed by the addition of ammonium formate (0.3 g) and 10% palladium on carbon (30 mg). The mixture was heated within a microwave for 180 minutes at 100° C. before being cooled to room temperature, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound (19 mg).

후처리

  1. temperaturebefore cooling to room temperature
  2. temperatureThe mixture was heated within a microwave for 180 minutes at 100° C.
  3. temperaturebefore being cooled to room temperature
  4. filtrationfiltered
  5. washwashed with ethanol
  6. concentrationThe filtrate was concentrated in vacuo
  7. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

출처 및 근거

ORD 기록
ord-dd8b406981be4fc1a2ec5bf8400936ea
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163905B2

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