Formaldehyde → HCID 86750812, compound

HRID 1780355Notes

Reaction equation

HRID 1780355 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[C:23](OC(C)(C)C)=O)[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1.C=O>C(O)=O>[ClH:15].[ClH:15].[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[CH3:23])[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 54192485HCID 54192485, compound

Product 1

HCID 86750812HCID 86750812, compoundYield 135.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from Example 81a (760 mg, 1.8 mmol) was added formalin (37%, 20 mL) and formic acid (10 mL), and the mixture was heated at 100° C. for 1 hours. The solvent was concentrated, and saturated aqueous NaHCO3 was added to the residue. At pH 8 the mixture was extracted with methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with methylene chloride:methanol 100:2-100:15 to afford to give the free base of the title compound (327 mg, 55% yield). MS (DCI/NH3) m/z 330 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.80 (m, 3H), 2.07 (m, 1H), 2.35 (m, 1H), 2.52 (s, 3H), 2.72 (m, 1H), 3.16 (m, 1H), 4.00 (m, 1H), 4.07 (m, 1H), 7.0 (m, 1H), 7.40 (m, 2H), 7.53 (m, 2H), 8.06 (m, 1H), 8.63 (m, 2H). The base was converted to the salt by treatment with HCl in ether to give the title compound. mp 220°-222° C. (dec). MS (DCI/NH3) m/z 330 (M+H)+. 1 H NMR (D2O, 300 MHz) δ: 2.06-2.37 (m, 3H), 2.44 (m, 1H), 3.07 (s, 3H), 3.30 (m, 1H), 3.78 (m, 1H), 3.98 (m, 1H), 4.42 (dd, J=6.1, 11.2 Hz, 1H), 4.58 (dd, J=3.0, 11.2 Hz, 1H), 7.35 (d, J=16.3 Hz, 1H), 7.82 (d, J=16.6 Hz, 1H), 7.87 (d, J=3.1 Hz, 1H), 8.03 (d, J=6.8 Hz, 2H), 8.11 (d, J=2.7 Hz, 1H), 8.63 (d, J=6.8 Hz, 2H). Anal. Calcd for C18H20N3OCl·2.2 HCl: C, 52.73; H, 5.46; N, 10.23. Found: C, 52.98; H, 5.56; N, 9.90. [α]25D =+11.48° (c 0.30, MeOH).

Workup

  1. concentrationThe solvent was concentrated
  2. additionsaturated aqueous NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with methylene chloride, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with methylene chloride:methanol 100:2-100:15
  8. customto afford

Sources & evidence

ORD record
ord-c877a332a0094812a158557bf35d00c3
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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