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 1007849

반응식

HRID 1007849 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-4bbe51b55a2545fd836e3c4f2bbaf334
출처 데이터셋
uspto-grants-2004_09
특허 번호
US06797709B2

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