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

반응식

HRID 431059 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-eebd32d1037f41cf8eb3b04a3f6438fd
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06656935B2

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