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

Reaction equation

HRID 1007849 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-4bbe51b55a2545fd836e3c4f2bbaf334
Source dataset
uspto-grants-2004_09
Patent number
US06797709B2

Linked notes

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