Diisopropylethylamine → 5-[(3R,5S)-4-(cyanomethyl)-3,5-dimethylpiperazin-1-yl]-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

HRID 1092104

反応式

HRID 1092104 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[NH:12][N:13]=[C:14]([O:16][CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=3)[CH:15]=2)=[O:9])=[N:6][CH:7]=1.CN1[C@@H](C)CNC[C@H]1C.[CH3:37][C@H:38]1[CH2:43][NH:42][CH2:41][C@@H:40]([CH3:44])[N:39]1[CH2:45][C:46]#[N:47].C(N(C(C)C)C(C)C)C>CS(C)=O.CO>[C:46]([CH2:45][N:39]1[C@@H:38]([CH3:37])[CH2:43][N:42]([C:2]2[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]3[NH:12][N:13]=[C:14]([O:16][CH2:17][C:18]4[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=4)[CH:15]=3)=[O:9])=[N:6][CH:7]=2)[CH2:41][C@H:40]1[CH3:44])#[N:47]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 30720221(2R,6S)-1,2,6-TrimethylpiperazineHCID 866210735-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamideHCID 866210742-[(2S,6R)-2,6-dimethylpiperazin-1-yl]acetonitrile

生成物 1

HCID 866210765-[(3R,5S)-4-(cyanomethyl)-3,5-dimethylpiperazin-1-yl]-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide収率 18.3%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 887Methanol溶媒

実験手順

5-Chloro-N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]pyrazine-2-carboxamide (273 mg, 0.70 mmol) was added in one portion to a 3:1 mixture of (2R,6S)-1,2,6-trimethylpiperazine and 2-[(2S,6R)-2,6-dimethylpiperazin-1-yl]acetonitrile (180 mg, 1.40 mmol) in anhydrous dimethylsulfoxide (1.40 ml) at 25° C. The resulting solution was stirred at ambient temperature for 2 h. The reaction was incomplete and N-ethyldiisopropylamine (0.24 ml, 1.40 mmol) was added and the solution was stirred at 60° C. for a further 2 h. The reaction mixture was diluted with methanol (20 mL) and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH to afford impure material. The concentrated eluent was purified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM. Pure fractions were evaporated to dryness to afford the title compound (65 mg, 18%) as a yellow solid.

後処理

  1. stirringthe solution was stirred at 60° C. for a further 2 h
  2. custompurified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. customto afford impure material
  5. customThe concentrated eluent was purified by silica column chromatography
  6. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM
  7. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-8c098303349b4235b86f67a30803f44a
出典データセット
uspto-grants-2012_03
特許番号
US08129391B2

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