4-Methylmorpholine → [4-({[2-(4-Fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

HRID 354098

反応式

HRID 354098 の反応式
[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[N:15]=[CH:14][CH:13]=[CH:12][C:8]=2[C:9]([OH:11])=O)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:40]([O:44][C:45](=[O:56])[NH:46][CH2:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54][NH2:55])=[CH:50][CH:49]=1)([CH3:43])([CH3:42])[CH3:41].CN1CCOCC1>CN(C)C=O>[C:40]([O:44][C:45](=[O:56])[NH:46][CH2:47][C:48]1[CH:49]=[CH:50][C:51]([CH2:54][NH:55][C:9]([C:8]2[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:17][CH:16]=3)=[N:15][CH:14]=[CH:13][CH:12]=2)=[O:11])=[CH:52][CH:53]=1)([CH3:43])([CH3:41])[CH3:42]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 6051232-(4-Fluorophenoxy)nicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3354775tert-butyl N-{[4-(aminomethyl)phenyl]methyl}carbamate

生成物 1

HCID 20738633[4-({[2-(4-Fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester収率 81.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

2-(4-Fluoro-phenoxy)-nicotinic acid (see reference Patent application WO 98/45268) (6.20 g, 26 mmol), 1-hydroxybenzotriazole (5.39 g, 40 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.62 g, 34 mmol) were disolved in N,N-dimethylformamide (50 ml) at room temperature and (4-aminomethyl-benzyl)-carbamic acid tert-butyl ester (6.28 g, 26 mmol) (see Preparation 1) added followed by addition of N-methyl morpholine (4.4 ml, 40 mmol). The reaction mixture was stirred under an atmosphere of nitrogen at room temperature for 18 hours, and then partitioned between ethyl acetate (100 ml) and water (100 ml) and the organic layer separated. The organic phase was then washed with a saturated aqueous solution of sodium chloride (100 ml), dried over anhydrous magnesium sulphate and the solvent removed in vacuo. The residue was triturated with diethylether (15 ml) giving [4-({[2-(4-fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (9.52 g) as an off-white solid.

後処理

  1. custompartitioned between ethyl acetate (100 ml) and water (100 ml)
  2. customthe organic layer separated
  3. washThe organic phase was then washed with a saturated aqueous solution of sodium chloride (100 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customthe solvent removed in vacuo
  6. customThe residue was triturated with diethylether (15 ml)

出典と根拠

ORDレコード
ord-9a573d39a2d34264b5aee21f5cfce8e7
出典データセット
uspto-grants-2004_06
特許番号
US06756392B2

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