Water → N-(5-(7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)pyridin-2-yl)acetamide

HRID 1910692Notes

Reaction equation

HRID 1910692 reaction equation
Cl[C:2]1[C:3]2[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=2[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:6](=[O:17])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:8]=1.[Li+].[Cl-].CC1(C)C(C)(C)OB([C:42]2[CH:43]=[CH:44][C:45]([NH:48][C:49](=[O:51])[CH3:50])=[N:46][CH:47]=2)O1.O>O1CCOCC1>[Cl:31][C:29]1[CH:28]=[CH:27][C:4]2[N:5]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:6](=[O:17])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:8]=[C:2]([C:42]3[CH:43]=[CH:44][C:45]([NH:48][C:49](=[O:51])[CH3:50])=[N:46][CH:47]=3)[C:3]=2[CH:30]=1

Participants

6

Reactant 4

HCID 962WaterHCID 433294Lithium ChlorideHCID 177502022-Acetamidopyridine-5-boronic acid pinacol esterHCID 595943935,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 67283418N-(5-(7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)pyridin-2-yl)acetamideYield 83.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (208 mg, 0.439 mmol), LiCl (56 mg, 1.32 mmol), and CsOH (221 mg, 1.32 mmol) were combined, then a solution of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (115 mg, 0.439 mmol) in 1,4-dioxane (3 mL) was added followed by water (300 uL). The mixture was purged with nitrogen, then tetrakis(triphenylphosphinepalladium(0) (51 mg, 0.044 mmol) was added and the flask was lowered into a 100° C. oil bath and heated at 100° C. for 3 h. The mixture was allowed to cool, then diluted with ethyl acetate and rinsed with water 2× then brine and dried (MgSO4). Chromatography eluting with 40-50% ethyl acetate in hexanes to give a colorless oil (210 mg, 83% yield). MS (ES+) m/z 573.1 (M+1).

Workup

  1. customThe mixture was purged with nitrogen
  2. additiontetrakis(triphenylphosphinepalladium(0) (51 mg, 0.044 mmol) was added
  3. customwas lowered into a 100° C.
  4. temperatureto cool
  5. additiondiluted with ethyl acetate
  6. washrinsed with water 2×
  7. dry with materialbrine and dried (MgSO4)
  8. washChromatography eluting with 40-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-086a62092f284368b6d3d708a4702ef5
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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