Potassium Phosphate, Tribasic → 4-(5-Cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acid

HRID 81078노트

반응식

HRID 81078 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH:5]=[C:4]([S:17][CH3:18])[C:3]=1[C:19]#[N:20].[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[CH:29]=[C:28](B(O)O)[CH:27]=[CH:26]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C(=O)C.CCOC(C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:19]([C:3]1[C:4]([S:17][CH3:18])=[CH:5][C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)=[N:7][C:2]=1[C:28]1[CH:27]=[CH:26][C:25]2[C:30](=[CH:31][CH:32]=[C:23]([O:22][CH3:21])[CH:24]=2)[CH:29]=1)#[N:20]

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 46416926-Methoxy-2-naphthaleneboronic acidHCID 866656994-(6-Chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid

생성물 1

HCID 669269734-(5-Cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acid수율 64.3%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

실험 절차

A mixture of 4-(6-chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid (50 mg, 0.164 mmol) and 6-methoxynaphthalen-2-ylboronic acid (49.7 mg, 0.246 mmol), potassium phosphate (139 mg, 0.656 mmol) and palladium tetrakis(triphenylphosphine) (18.96 mg, 0.016 mmol) in N,N-dimethylacetamide (2 mL) was pumped under vacuum and backfilled with nitrogen three times. After 2 h at 100° C., the mixture was cooled to room temperature, diluted with EtOAc (60 mL), washed with saturated NH4Cl (5 mL), water (5 ml), brine (5 mL), dried (MgSO4) and concentrated. The residue was triturated with MeOH (10 ml) and filtered. The yellow solid was collected and dried under vacuum to give 4-(5-cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acid (45 mg, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.34-8.53 (2H, m), 8.21-8.34 (1H, m), 7.99-8.19 (4H, m), 7.85-7.98 (1H, m), 7.41-7.54 (1H, m), 7.18-7.37 (2H, m), 3.94 (3H, s); MS (ES+) m/z: 427 (M+H); LC retention time: 4.01 min (analytical HPLC Method A).

후처리

  1. washwashed with saturated NH4Cl (5 mL), water (5 ml), brine (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was triturated with MeOH (10 ml)
  5. filtrationfiltered
  6. customThe yellow solid was collected
  7. customdried under vacuum

출처 및 근거

ORD 기록
ord-05176bd0a2e54b849d7ebc12a89cb60a
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846673B2

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