Triethylamine hydrochloride → Irbesartan

HRID 659755

반응식

HRID 659755 반응식
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]#[N:24])=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:29][CH2:28][CH2:27][CH2:26]2)[N:6]=1)[CH2:2][CH2:3][CH3:4].[N-:30]=[N+:31]=[N-:32].[Na+].Cl.C(N(CC)CC)C.[OH-].[Na+]>CN(C)C=O.O>[CH3:4][CH2:3][CH2:2][CH2:1][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:32]=[N:31][NH:30][N:24]=3)=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:26][CH2:27][CH2:28][CH2:29]2)[N:6]=1

참가 물질

7

반응물 4

HCID 11130Triethylamine hydrochlorideHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 98431164'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

생성물 1

HCID 3749Irbesartan수율 95%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 2-n-butyl-3-[(2′-cyanobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-en-4-one (10 g), sodium azide (7.7 g) and triethylamine hydrochloride (7.1 g) in N,N-dimethylformamide (30 ml) was refluxed for 14 hours under stirring. The reaction was cooled to room temperature and 20 ml water was added. The reaction mixture was adjusted to pH of about 12 using 10% NaOH solution. The alkaline solution was washed with toluene (15 ml) and the aqueous phase was neutralized to pH of 6.5 using concentrated HCl. The resulting suspension was stirred for 3 hours at room temperature and filtered to obtain irbesartan (3.4 g, 95% purity by HPLC). Recrystallization of the product using ethanol results in 3.05 g of irbesartan with 99.2% purity and content of the impurity 2-n-butyl-3-[(2′-carboxamidobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-en-4-one: 0.09%.

후처리

  1. temperaturewas refluxed for 14 hours
  2. washThe alkaline solution was washed with toluene (15 ml)
  3. stirringThe resulting suspension was stirred for 3 hours at room temperature
  4. filtrationfiltered

출처 및 근거

ORD 기록
ord-88d06e44cbbc4a08b80e3b57e331ef71
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08080670B2

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