Toluene → HCID 18511070, compound

HRID 635754Notes

Reaction equation

HRID 635754 reaction equation
[CH3:1][C:2]1[NH:7][C:6]2=[CH:8][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:10][C:5]2=[C:4]([Cl:17])[N:3]=1.[OH:18][CH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][NH:21]1.O=P(Cl)(Cl)Cl.C1(C)C=CC=CC=1>CN1CCOCC1>[OH2:18].[ClH:17].[CH3:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]3[C:5]2=[C:4]([N:21]2[CH:20]([CH2:19]3)[CH2:25][CH2:24][CH2:23][CH2:22]2)[N:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 24813Phosphorus oxychlorideHCID 94263Piperidin-2-ylmethanolHCID 178432852HCID 178432852, compound

Product 1

HCID 18511070HCID 18511070, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 79724-MethylmorpholineSolvent

Procedure

A solution of 2-methyl-4-chloro-6-phenyl pyrrolo[3,2-d]pyrimidine (1.0 g, 4.1 mmol, Example 1e) and 2-hydroxymethyl piperidine (Aldrich Chemical Company) (0.49 g, 4.2 mmol) in N-methyl morpholine (10 mL) was heated at 110° C. for 12 h. The solvent was concentrated in vacuo and the residue was mixed with POCl3 (5 mL, 54 mmol) and toluene (20 mL). The mixture was heated at reflux for 6.5 h before it was concentrated in vacuo. The residue was taken up in CH2Cl2 (50 mL)-H2O (50 mL) and the pH of the aqueous phase was adjusted to pH˜8 with NaOH solution (2 N). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (3×). The combinbed organic phase was dried over Na2SO4, concentrated in vacuo, and the resulting residue was purified by flash chromatography on silica gel (MeOH in CH2Cl2, 1-15%). The free base was treated with ethereal HCl to give the title compound as the HCl salt (0.18 g, 14%). Mp: >280° C. 1H NMR (DMSO-d6; 500 MHz): d 1.58-1.66 (m, 3), 1, 85-1.91 (m, 2), 2.05 (d, 1, J=10), 2.55 (s, 3), 3.43 (t, 1, J=10), 4.22-4.25 (m, 2), 4.77 (t, 1, J=14), 4.86(d, 1, J=13), 7.10 (s, 1), 7.49-7.57 (m, 3), 8.02 (d, 2, J=8). MS m/z: 305 (M+1). Anal. Calcd for C19H20N4.2HCl.H2O: C, 57.72; H, 6.12; N, 14.18; Cl, 17.95. Found: C, 57.69; H, 6.24; N, 14.02; Cl, 17.79.

Workup

  1. concentrationThe solvent was concentrated in vacuo
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 6.5 h before it
  4. concentrationwas concentrated in vacuo
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with CH2Cl2 (3×)
  7. dry with materialThe combinbed organic phase was dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customthe resulting residue was purified by flash chromatography on silica gel (MeOH in CH2Cl2, 1-15%)
  10. additionThe free base was treated with ethereal HCl

Sources & evidence

ORD record
ord-4660181ad5da464da6185d406a338cf8
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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