Hydrochloric Acid → HCID 178490288, 화합물

HRID 216175

반응식

HRID 216175 반응식
COC1C=CC=CC=1CO.[H-].[Na+].[Cl:13]C1N=C(OC)N=C(NCCC2C=CC(OC)=CC=2)C=1.C[O:34][C:35]1[N:40]=[C:39]([NH:41][CH2:42][CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=2)[CH:38]=[C:37]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=2[O:60][CH3:61])[N:36]=1.COC1C=CC=CC=1COC1N=C(NCCC2C=CC(OC)=CC=2)C=C(OCC2C=CC=CC=2OC)N=1.Cl>CN(C=O)C.O.C(Cl)Cl.CCOC(C)=O>[ClH:13].[CH3:61][O:60][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=1[CH2:53][O:52][C:37]1[CH:38]=[C:39]([NH:41][CH2:42][CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=2)[N:40]=[C:35]([OH:34])[N:36]=1

참가 물질

11

반응물 6

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 691542-Methoxybenzyl alcoholHCID 53323153HCID 53323153, 화합물HCID 57636025(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxyphenyl)-ethyl]amine2회HCID 69070250HCID 69070250, 화합물

생성물 1

HCID 178490288HCID 178490288, 화합물수율 19%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of (2-Methoxy-phenyl)-methanol (860 mg, 6.22 mmol), and sodium hydride (60%, 0.3 g) in DMF (10 mL) is add (6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine [0.54 g, 1.8 mmol, Intermediate (8)] at 10° C. After 1 h at 60° C., the mixture is diluted with H2O, and extracted with ethyl acetate. The extracts are dried (MgSO4), filtered, concentrated, and chromatographed (SiO2, 40% EtOAc in Heptane) to afford a non-separable mix of the product, [2-Methoxy-6-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine, and the disubstituted side product, [2,6-Bis-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine. To above mixture in CH2Cl2 is added a solution of HCl in EtOAc, and the mixture is concentrated, triturated (ether), and filtered to give 141 mg (19%) of 4-(2-Methoxy-benzyloxy)-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-2-ol hydrochloride as a solid. LCMS: RT=2.07 minutes, MS: 382 (M+H). The filtrate is concentrated, and chromatographed (silica gel, 40% EtOAc in Heptane) to afford [2-Methoxy-6-(2-methoxy-benzyloxy)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride [39 mg, 5%, Example (48)] as an oil. LCMS: RT=3.3 minutes, MS: 396 (M+H). IC50=12 nM

후처리

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extracts are dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customchromatographed (SiO2, 40% EtOAc in Heptane)
  6. customto afford
  7. concentrationthe mixture is concentrated
  8. customtriturated (ether)
  9. filtrationfiltered

출처 및 근거

ORD 기록
ord-fa9a37255da2416ba307759acfcddf78
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193183B2

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