Hydrochloric Acid → N-(5-bromo-3-phenoxypyridin-2-yl)-4-(1-methylpiperidin-4-yl)thiazol-2-amine dihydrochloride

HRID 911804노트

반응식

HRID 911804 반응식
[ClH:1].Cl.[Br:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[N:15]=2)=[N:8][CH:9]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:33](C)=O.[Na+].C([O-])(O)=O.[Na+].Cl>C(Cl)CCl>[ClH:1].[ClH:1].[Br:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]3[CH2:21][CH2:20][N:19]([CH3:33])[CH2:18][CH2:17]3)[N:15]=2)=[N:8][CH:9]=1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 866314825-bromo-3-phenoxy-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine dihydrochloride

생성물 1

HCID 86631483N-(5-bromo-3-phenoxypyridin-2-yl)-4-(1-methylpiperidin-4-yl)thiazol-2-amine dihydrochloride수율 123.5%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a mixture of 5-bromo-3-phenoxy-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine dihydrochloride (80 mg, 0.16 mmol), paraformaldehyde (7.15 mg, 0.24 mmol), and ClCH2CH2Cl (2 mL) was added NaBH(OAc)3 (134 mg, 0.64 mmol) and the reaction was stirred at ambient temperature for 2 days. Poured into saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (10% methanol in EtOAc with 0.2% NH3) to afford the title compound (51.2 mg, 62.3% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 11.00 (bs, 1H), 10.22 (bs, 1H), 8.23 (s, 1H), 7.48-7.38 (m, 3H), 7.22 (t, 1H), 7.12 (m, 2H), 6.77 (s, 1H), 3.46 (m, 2H), 3.05 (m, 2H), 2.82 (m, 1H), 2.74 (d, 3H), 2.14 (m, 2H), 1.88 (m, 2H). Mass spectrum (apci) m/z=445.3 (4+H-2HCl).

후처리

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel (10% methanol in EtOAc with 0.2% NH3)

출처 및 근거

ORD 기록
ord-150dcb0c8635417f9d7010251dfdf858
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022223B2

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