Hydrochloric Acid → 7-Bromo-3-methyl-5-pyridin-2-yl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

HRID 75260Notes

Reaction equation

HRID 75260 reaction equation
C(OC(=O)[NH:7][CH:8]([C:10](=[O:27])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=1[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=O)[CH3:9])(C)(C)C.Cl>C(Cl)(Cl)Cl>[Br:18][C:15]1[CH:16]=[CH:17][C:12]2[NH:11][C:10](=[O:27])[CH:8]([CH3:9])[N:7]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[C:13]=2[CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68526704HCID 68526704, compound

Product 1

HCID 685270487-Bromo-3-methyl-5-pyridin-2-yl-1,3-dihydro-benzo[e][1,4]diazepin-2-oneYield 80%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of ester 124 (16 g, 35.69 mmol) in CHCl3 (300 mL) at rt, hydrogen chloride gas was added in slowly. After 20 min, the addition was stopped and the solution was allowed to stir overnight at rt. The reaction mixture was washed with a saturated solution of sodium bicarbonate (2×50 mL) and water (2×50 mL). The organic layer was concentrated under reduced pressure. The residual oil was dissolved in methanol-water (3:1, 300 mL) and the pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N). The reaction mixture was stirred for 10 h at rt. The solution was concentrated under reduced pressure and water (80 mL) was added. The solution was extracted with CH2Cl2 (3×70) and concentrated under reduced pressure. The crude solid 125 was purified by recrystallization from methanol/water to provide pure 125 (9.42 g, 80%). mp 227-229° C.; IR (KBr, cm−1) 2928, 1684, 1611, 1476; 1H NMR (CDCl3) δ 9.47 (bs, 1 H), 8.62 (d, J=4.7 Hz, 1 H), 8.0 (d, J=7.90 Hz, 1 H), 7.81 (td, J=7.7, 1.6 Hz, 1 H), 7.56 (dd, J=8.6, 2.2 Hz 1 H), 7.50 (dd, J=2.1 Hz, 1 H), 7.36 (dd, J=7.4 Hz, 1 H), 7.06 (d, J=8.6 Hz, 1 H), 3.85 (q, J=6.5 Hz, 1 H), 1.76 (d, J=6.5 Hz, 3 H); MS (EI) m/e (relative intensity) 330 (M+, 50), 329 (50), 314 (52), 288 (100), 250 (30), 208 (32), 179(50), 88(72); [α]26D=403.2 (c 0.50, EtOAc).

Workup

  1. additionthe addition
  2. washThe reaction mixture was washed with a saturated solution of sodium bicarbonate (2×50 mL) and water (2×50 mL)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. dissolutionThe residual oil was dissolved in methanol-water (3:1, 300 mL)
  5. additionthe pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N)
  6. stirringThe reaction mixture was stirred for 10 h at rt
  7. concentrationThe solution was concentrated under reduced pressure and water (80 mL)
  8. additionwas added
  9. extractionThe solution was extracted with CH2Cl2 (3×70)
  10. concentrationconcentrated under reduced pressure
  11. customThe crude solid 125 was purified by recrystallization from methanol/water

Sources & evidence

ORD record
ord-5fb05200228d4f41bf89179ebce1f9ad
Source dataset
uspto-grants-2014_09
Patent number
US08835424B2

Reaction notes

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