Triethylamine → HCID 178422067, compound

HRID 1371190Notes

Reaction equation

HRID 1371190 reaction equation
[CH3:1][CH:2]1[CH2:7][CH:6]([C:8]2[NH:13][C:12]3=[C:14]([CH3:25])[C:15]([C:17]4[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=4)=[N:16][C:11]3=[CH:10][N:9]=2)[CH2:5][CH2:4][NH:3]1.B(Br)(Br)Br.CCN(CC)CC>C(Cl)Cl>[CH3:1][CH:2]1[CH2:7][CH:6]([C:8]2[NH:13][C:12]3=[C:14]([CH3:25])[C:15]([C:17]4[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=4)=[N:16][C:11]3=[CH:10][N:9]=2)[CH2:5][CH2:4][NH:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 25134Boron tribromideHCID 178488896HCID 178488896, compound

Product 1

HCID 178422067HCID 178422067, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a −78° C. solution of 1-[2,7-dimethyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]-4-methoxybenzene (Example 136) (0.45 g, 1.34 mmol) in CH2Cl2 (20 mL) under a N2 atmosphere was added 1 M BBr3 (2.6 mL, 2.60 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 (2 mL). The resulting mixture was stirred at room temperature for 2 h. The mixture 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 272 mg (64%) of 4-[2,7-dimethyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]phenol as a beige colored solid. This compound (272 mg, 0.80 mmol) was dissolved in 4:2:1 EtOAc/MeOH/CH2Cl2 (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.80 mL, 0.80 mmol). The solution was allowed to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×5 mL) and dried under vacuum at 60° C. to give 107 mg (23%) of the title compound as brown colored crystals. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.61 (br s, 6), 2.24 (s, 3), 2.54 (s, 3), 3.93 (br s, 4), 6.91 (d, 2, J=8.1), 7.43 (d, 2, J=8.4), 9.96 (s, 1), 11.70 (s, 1), 13.94 (s, 1). MS m/z: 323 (M+1 for free base). Anal. Calcd for C19H22N4O.HCl.0.75H2O: C, 61.28; H, 6.63; N, 15.05; Cl, 9.52. Found: C, 61.32; H, 6.62; N, 14.96; Cl, 9.45.

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 mixture was transferred to a separatory funnel
  4. customThe organic solution was separated
  5. washwashed with H2O (100 mL), saturated NaCl (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3f7089e3bced4d11badae53324128afa
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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