Triethylamine → HCID 67242423, 화합물

HRID 1770402노트

반응식

HRID 1770402 반응식
[F:1][CH:2]([F:15])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([OH:14])=O)[N:4]=1.C(Cl)(=O)C(Cl)=O.[Cl-].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[C:25]=1[CH:31]1[O:35][N:34]=[C:33]([C:36]2[N:37]=[C:38]([CH:41]3[CH2:46][CH2:45][NH2+:44][CH2:43][CH2:42]3)[S:39][CH:40]=2)[CH2:32]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[F:15][CH:2]([F:1])[C:3]1[CH:7]=[C:6]([CH:8]([F:9])[F:10])[N:5]([CH2:11][C:12]([N:44]2[CH2:45][CH2:46][CH:41]([C:38]3[S:39][CH:40]=[C:36]([C:33]4[CH2:32][CH:31]([C:25]5[C:26]([OH:30])=[CH:27][CH:28]=[CH:29][C:24]=5[Cl:23])[O:35][N:34]=4)[N:37]=3)[CH2:42][CH2:43]2)=[O:14])[N:4]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 12298443,5-Bis(difluoromethyl)-1H-pyrazole-1-acetic acidHCID 67238250HCID 67238250, 화합물

생성물 1

HCID 67242423HCID 67242423, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (177 mg) in dichloromethane (40 ml) are added, at 0° C., oxalyl chloride (290 mg) and one drop of N,N-dimethylformamide. The reaction mixture is stirred at room temperature for 2 hours. The solvent and the excess reagent are removed under reduced pressure. The solid residue is again dissolved in dichloromethane and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (25 ml). The reaction mixture is stirred at room temperature overnight. Then it is admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. Purification by column chromatography gives 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (110 mg).

후처리

  1. customThe solvent and the excess reagent are removed under reduced pressure
  2. dissolutionThe solid residue is again dissolved in dichloromethane and, at 0° C.
  3. stirringThe reaction mixture is stirred at room temperature overnight
  4. customthe aqueous phase is removed
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic phases are dried over sodium sulphate
  7. concentrationconcentrated
  8. customPurification by column chromatography

출처 및 근거

ORD 기록
ord-a164863e395a40cb8e57581520960bd8
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09247748B2

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