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

HRID 1697285ノート

反応式

HRID 1697285 の反応式
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

参加物

10

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-dd8b406981be4fc1a2ec5bf8400936ea
出典データセット
uspto-grants-2012_04
特許番号
US08163905B2

反応ノート

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