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

HRID 1806049ノート

反応式

HRID 1806049 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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 (M+H-2HCl).

後処理

  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)

出典と根拠

ORDレコード
ord-ce2dd9b5a6f24483aa8e50dbfe8cc1c3
出典データセット
uspto-grants-2013_01
特許番号
US08354540B2

反応ノート

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