Acetic Acid → 3-Amino-5-(3-fluorophenyl)-9-(hydroxymethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 921273Notes

Reaction equation

HRID 921273 reaction equation
C(OC(=O)[NH:10][CH:11]1[C:17](=[O:18])[NH:16][C:15]2[C:19]([CH2:23][O:24][Si](C(C)(C)C)(C)C)=[CH:20][CH:21]=[CH:22][C:14]=2[C:13]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[N:12]1)C1C=CC=CC=1.CC(O)=O.CCOCC>Br>[NH2:10][CH:11]1[C:17](=[O:18])[NH:16][C:15]2[C:19]([CH2:23][OH:24])=[CH:20][CH:21]=[CH:22][C:14]=2[C:13]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[N:12]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 86713392Benzyl (9-(((tert-butyldimethylsilyl)oxy)methyl)-5-(3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate

Product 1

HCID 867133933-Amino-5-(3-fluorophenyl)-9-(hydroxymethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 95.4%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

A mixture of Intermediate 37G (255 mg, 0.466 mmol) in 33% HBr in HOAc (1149 μl, 6.98 mmol) was stirred at room temperature for 1 h. Ether was added and the resulting solid precipitate was collected by filtration and rinsed with ether. The solid was dissolved in MeOH (10 mL) and K2CO3 (1.3 g) was added. The mixture was stirred for 40 min. and then filtered and concentrated to dryness to afford Intermediate 37H (133 mg). HPLC: RT=1.102 min (CHROMOLITH® SpeedROD column 4 6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 mL/min, monitoring at 220 nm), MS(ES): m/z=300.2 [M+H+].

Workup

  1. filtrationthe resulting solid precipitate was collected by filtration
  2. washrinsed with ether
  3. dissolutionThe solid was dissolved in MeOH (10 mL)
  4. additionK2CO3 (1.3 g) was added
  5. stirringThe mixture was stirred for 40 min.
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-ba83c65aefdc45fd9bebc8d3b8b6aeaa
Source dataset
uspto-grants-2016_03
Patent number
US09273014B2

Reaction notes

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