1,3,5-trimethyl-1H-pyrazol-4-amine → (S)-2-(2-hydroxymethyl-1-pyrrolidin-yl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(1,3,5-trimethyl-4-pyrazolyl)carbamoyl]pyrimidine

HRID 431059

反応式

HRID 431059 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[CH2:5][NH:6][C:7]1[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]([N:16]2[CH2:20][CH2:19][CH2:18][C@H:17]2[CH2:21][OH:22])[N:8]=1.[NH2:28][C:29]1[C:30]([CH3:36])=[N:31][N:32]([CH3:35])[C:33]=1[CH3:34].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O>[OH:22][CH2:21][C@@H:17]1[CH2:18][CH2:19][CH2:20][N:16]1[C:9]1[N:8]=[C:7]([NH:6][CH2:5][C:4]2[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:2]([Cl:1])[CH:3]=2)[C:12]([C:13](=[O:15])[NH:28][C:29]2[C:30]([CH3:36])=[N:31][N:32]([CH3:35])[C:33]=2[CH3:34])=[CH:11][N:10]=1

参加物

7

反応物 5

HCID 1616031,3,5-trimethyl-1H-pyrazol-4-amineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 671193354-[(3-Chloro-4-methoxybenzyl)amino]-2-[(2S)-2-(hydroxymethyl)-pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

生成物 1

HCID 10278631(S)-2-(2-hydroxymethyl-1-pyrrolidin-yl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(1,3,5-trimethyl-4-pyrazolyl)carbamoyl]pyrimidine収率 90.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of (S)-4-(3-chloro-4-methoxybenzylamino)-5-carboxy-2-(2-hydroxymethyl-1-pyrrolidinyl)pyrimidine (100 mg) obtained in Example 1-(4), 4-amino-1,3,5-trimethylpyrazole (47.9 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (58.7 mg), 1-hydroxybenzotriazole monohydrate (41.3 mg), and N,N-dimethylformamide (3 ml) is stirred at room temperature for 8 hours, and poured into aqueous sodium hydrogen carbonate solution. The mixture is extracted with ethyl acetate, and the organic layer is washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (solvent; chloroform:methanol=5:1) to give (S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(1,3,5-trimethyl-4-pyrazolyl)carbamoyl]pyrimidine (115 mg), MS (m/z): 500 (MH+).

後処理

  1. extractionThe mixture is extracted with ethyl acetate
  2. washthe organic layer is washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent is evaporated under reduced pressure
  5. customthe residue is purified by silica gel column chromatography (solvent; chloroform:methanol=5:1)

出典と根拠

ORDレコード
ord-eebd32d1037f41cf8eb3b04a3f6438fd
出典データセット
uspto-grants-2003_12
特許番号
US06656935B2

関連ノート

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