Formaldehyde → HCID 86750809, 화합물

HRID 365847노트

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HRID 365847 반응식
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16](OC(C)(C)C)=O)[CH:5]=[N:6][C:7]=1[Cl:8].C=O>C(O)=O>[ClH:8].[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[CH3:16])[CH:5]=[N:6][C:7]=1[Cl:8]

참가 물질

4

반응물 2

HCID 712FormaldehydeHCID 22872666HCID 22872666, 화합물

생성물 1

HCID 86750809HCID 86750809, 화합물수율 119.1%

시약·촉매·용매 1

HCID 284Formic Acid용매

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온도
70 °C

실험 절차

To 5-bromo-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 69a (210 mg, 0.54 mmol) was added formalin (37%, 7 mL) and formic acid (3.5 mL), and the mixture was heated at 70° C. for 2.5 hours. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2 :MeOH 100:5-100:10 to afford to give the free base of the title compound (110 mg, 67% yield). MS (CI/NH3) m/z 305/307 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.68 (m, 3H), 2.02 (m, 1H), 2.32 (m, 1H), 2.48 (s, 3H), 2.67 (m, 1H), 3.12 (m, 1H), 3.96 (m, 2H), 7.52 (m, 1H), 8.06 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in THF to give the title compound. MS (C NH3) m/z 305/307 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.20-2.17 (m, 2H), 2.18-2.31 (m, 1H), 2.32-2.47 (m, 1H), 3.03 (s, 3H), 3.27 (m, 1H), 3.73 (m, 1H), 3.96 (m, 1H), 4.36 (dd, J=6.1, 11.2 Hz, 1H), 4.53 (dd, J=3.1, 11.2 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 8.13 (d, J=2.7 Hz, 1H). Anal. Calcd for C11H14N2OBrCl·1.1 HCl: C, 38.22; H, 4.40; N, 8.10. Found: C, 37.95; H, 4.81; N, 7.76. [α]25D=+11.06° (c 0.24, MeOH).

후처리

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with CH2Cl2, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with CH2Cl2 :MeOH 100:5-100:10
  8. customto afford

출처 및 근거

ORD 기록
ord-30cdab254c964aa683bfee0ec2edc8bc
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06127386

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