Acetic Acid → 3-azido-7-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

HRID 2223089Notes

Reaction equation

HRID 2223089 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:11][C:12]1[CH:13]=[CH:14][C:15]2[N:21]([CH3:22])[C:20](=[O:23])[CH2:19][N:18]=[C:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:16]=2[CH:30]=1.CC(C1C=C(C(C)C)C(S([N:46]=[N+:47]=[N-:48])(=O)=O)=C(C(C)C)C=1)C.C(O)(=O)C>>[N:46]([CH:19]1[N:18]=[C:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:16]2[CH:30]=[C:12]([F:11])[CH:13]=[CH:14][C:15]=2[N:21]([CH3:22])[C:20]1=[O:23])=[N+:47]=[N-:48]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 443661797-Fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 597138183-azido-7-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-oneYield 83%

Procedure

As illustrated in the scheme above and following General Procedure 6, KHMDS (1.34 mL of 0.5 M in toluene, 0.670 mmol), 7-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (0.171 g, 0.637 mmol), trisyl azide (0.493 g, 1.59 mmol) and acetic acid (0.16 mL, 2.8 mmol) were combined. After workup, purification of the crude product by silica gel column chromatography (100% CH2Cl2 to 9:1 CH2Cl2:EtOAc) provided the title compound as a pale yellow solid (0.163 g, 83%). 1H-NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.54-7.49 (m, 1H), 7.47-7.42 (m, 2H), 7.39 (dd, J=4.8 Hz, J=9.2 Hz, 1H), 7.36-7.30 (m, 1H), 7.08 (dd, J=2.8 Hz, J=8.4 Hz, 1H), 4.55 (s, 1H), 3.45 (s, 3H). MS (ESI) (M+H)+=310.

Workup

  1. customAfter workup, purification of the crude product by silica gel column chromatography (100% CH2Cl2 to 9:1 CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-858e433fb765491c822889ef18941542
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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