Hydrochloric Acid → HCID 178525575, 화합물

HRID 70850노트

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HRID 70850 반응식
C([O:3][C:4](=[O:35])[CH2:5][C@H:6]([NH:20][C:21]([C:23]1[N:27](CC2C=CC=CC=2)[N:26]=[N:25][N:24]=1)=[O:22])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)C.C(OC(=O)C[C@H](NC(C1N=NN(CC2C=CC=CC=2)N=1)=O)CC1C=CC(C2C=CC=CC=2)=CC=1)C.[Li+].[OH-].Cl>CCO.C1COCC1>[C:11]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=[CH:9][C:8]([CH2:7][C@@H:6]([NH:20][C:21]([C:23]2[NH:27][N:26]=[N:25][N:24]=2)=[O:22])[CH2:5][C:4]([OH:35])=[O:3])=[CH:13][CH:12]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59607597HCID 59607597, 화합물HCID 67208758(R)-3-[(2-benzyl-2H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester

생성물 1

HCID 178525575HCID 178525575, 화합물

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a mixture of (R)-3-[(1-benzyl-1H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester and (R)-3-[(2-benzyl-2H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester (180 mg, 0.383 mmol) in EtOH (1 mL) and THF (1 mL) is added aqueous 1M LiOH (2 mL). After stirring for 0.5 hour, the reaction mixture is acidified with aqueous 1M HCl. The mixture is extracted with ethyl acetate, dried over Na2SO4, and concentrated under reduced pressure. The residue is dissolved in MeOH and hydrogenated with 10% Pd/C at room temperature for 3 hours and at 40° C. for 2 hours. The reaction mixture is concentrated and purified by reverse phase HPLC to give (R)-4-biphenyl-4-yl-3-[(1H-tetrazole-5-carbonyl)-amino]-butyric acid. HPLC retention time=1.18 minutes (condition D); MS (m+1)=352; 1H NMR (400 MHz, DMSO-d6) ppm 2.56 (dd, J=5.81, 15.92 Hz, 1H), 2.67 (dd, J=7.58, 15.92 Hz, 1H), 2.85-2.99 (m, 2H), 4.55-4.64 (m, 1H), 7.26-7.35 (m, 3H), 7.43 (dd, J=7.83, 7.83 Hz, 2H), 7.56 (d, J=8.08 Hz, 2H), 7.62 (d, J=7.07 Hz, 2H), 9.28 (d, 8.84 Hz, 1H), 12.28 (s, 1H).

후처리

  1. extractionThe mixture is extracted with ethyl acetate
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is dissolved in MeOH and hydrogenated with 10% Pd/C at room temperature for 3 hours and at 40° C. for 2 hours
  5. concentrationThe reaction mixture is concentrated
  6. custompurified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-90a791560fb64dd3b70fcb8ca0532265
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822534B2

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