HCID 67282441, compound → HCID 67282594, compound

HRID 1910704Notes

Reaction equation

HRID 1910704 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7](=[O:29])[CH:8]([CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=3)[N:9]=[C:10]([N:11]3[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]3)[C:4]=2[CH:3]=1.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([Mg]Br)=[CH:36][CH:35]=1>O1CCCC1>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7](=[O:29])[CH:8]([CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=3)[N:9]=[C:10]([N:11]3[CH2:12][CH2:13][C:14]([OH:17])([C:37]4[CH:38]=[CH:39][C:34]([O:33][CH3:32])=[CH:35][CH:36]=4)[CH2:15][CH2:16]3)[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 67282441HCID 67282441, compoundHCID 178491912HCID 178491912, compound

Product 1

HCID 67282594HCID 67282594, compoundYield 46.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7-Chloro-3-(naphthalen-2-ylmethyl)-5-(4-oxopiperidin-1-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (18 mg, 0.04 mmol) was dissolved in anhydrous tetrahydrofuran (0.2 mL) under nitrogen, 4-methoxyphenylmagnesium bromide (0.5M solution in tetrahydrofuran, 0.5 mL, 0.25 mmol) was added dropwise. After stirring at ambient temperature for 1 hour the reaction was quenched with water (1 mL), diluted with ethyl acetate, separated, washed with water, dried with sodium sulfate, decanted, and concentrated. The residue was redissolved in ethyl acetate (0.5 mL) and hexanes added slowly (total of 6 mL). A solid precipitated and was collected by filtration. Washing with hexanes provided 7-chloro-5-(4-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (10 mg, 43% yield). ESI m/z measured 540.2062 [M+H]+. calculated 540.2054.

Workup

  1. customwas quenched with water (1 mL)
  2. additiondiluted with ethyl acetate
  3. customseparated
  4. washwashed with water
  5. dry with materialdried with sodium sulfate
  6. customdecanted
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in ethyl acetate (0.5 mL)
  9. additionhexanes added slowly (total of 6 mL)
  10. customA solid precipitated
  11. filtrationwas collected by filtration
  12. washWashing with hexanes

Sources & evidence

ORD record
ord-55b5312d604949e4bb81f7c85a0985f5
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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