Triethylamine → HCID 178423292, compound

HRID 1371175Notes

Reaction equation

HRID 1371175 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:23]=[C:11]3[NH:12][C:13]([CH:16]4[CH2:21][CH2:20][NH:19][CH:18]([CH3:22])[CH2:17]4)=[N:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:4][C:3]=1[O:24]C.B(Br)(Br)Br.CCN(CC)CC>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:23]=[C:11]3[NH:12][C:13]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=4)=[N:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:4][C:3]=1[OH:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 25134Boron tribromideHCID 178488443HCID 178488443, compound

Product 1

HCID 178423292HCID 178423292, compoundYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a −78° C. solution of 2-fluoro-1-methoxy-4-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene (Example 119) (0.80 g, 2.35 mmol) in CH2Cl2 (40 mL) under a N2 atmosphere was added 1 M BBr3 (4.7 mL, 4.70 mmol). The reaction mixture was allowed to warm to room temperature. The mixture was stirred at room temperature for an additional 20 h. The reaction mixture was then poured onto ice-water (200 mL) and the pH of the aqueous solution was adjusted to pH 9 with the addition of NEt3 (4 mL). The resulting mixture was stirred at room temperature for 2 h. The solid which formed was removed by filtration and dicarded. The remaining solution was transferred to a separatory funnel. The organic solution was separated, washed with H2O (100 mL), saturated NaCl (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to afford 483 mg (62%) of 2-fluoro-4-(2-methyl-4-pyridylpyrrolo[4,5-d]pyrimidin-6-yl)phenol as a pale yellow colored solid. This compound (481 mg, 1.50 mmol) was dissolved in 4:2:1 EtOAc/MeOH/CH2Cl2 (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 mmol). The solution was allowed to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 315 mg (37%) of the title compound as a pale yellow colored solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.63 (br s, 6), 2.49 (s, 3), 3.96 (br s, 4), 6.76 (s, 1), 7.06 (dt, 1, J=1.9, 8.7), 7;58 (d, 1, J=8.5), 7.83 (dd, 1, J=1.9, 12.5), 10.47 (s, 1), 11.79 (s, 1), 14.12 (s, 1). MS m/z: 327 (M+1 for free base). Anal. Calcd for C18H19FN4O.HCl.1.5H2O: C, 55.45; H, 5.95; N, 14.37; Cl, 9.09. Found: C, 55.49; H, 5.87; N, 14.07; Cl, 9.03.

Workup

  1. additionThe reaction mixture was then poured onto ice-water (200 mL)
  2. stirringThe resulting mixture was stirred at room temperature for 2 h
  3. customThe solid which formed
  4. customwas removed by filtration
  5. customThe remaining solution was transferred to a separatory funnel
  6. customThe organic solution was separated
  7. washwashed with H2O (100 mL), saturated NaCl (100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-04d6ce8fc1ed4e05b8db5139c8436364
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

Loading…