Diazepam → HCID 67514039, compound

HRID 473927Notes

Reaction equation

HRID 473927 reaction equation
Cl[C:2]([N:4]1[CH2:10][C:9]2[CH:11]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]4[N:22]=[CH:21][N:20](C(OC(C)(C)C)=O)[C:19]=4[CH:30]=3)[CH:13]=[CH:14][C:8]=2[O:7][CH2:6][CH2:5]1)=[O:3].[N:31]1([C:37]2[N:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.[CH3:43]N1C2C=CC(Cl)=CC=2C(C2C=CC=CC=2)=NCC1=O>C(Cl)Cl>[CH3:43][C:21]1[NH:20][C:19]2[CH:30]=[C:15]([C:12]3[CH:13]=[CH:14][C:8]4[O:7][CH2:6][CH2:5][N:4]([C:2]([N:34]5[CH2:35][CH2:36][N:31]([C:37]6[N:38]=[CH:39][CH:40]=[CH:41][N:42]=6)[CH2:32][CH2:33]5)=[O:3])[CH2:10][C:9]=4[CH:11]=3)[CH:16]=[CH:17][C:18]=2[N:22]=1

Participants

5

Reactant 3

HCID 3016DiazepamHCID 887471-(2-Pyrimidinyl)piperazineHCID 86672019HCID 86672019, compound

Product 1

HCID 67514039HCID 67514039, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 6-[4-(chlorocarbonyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazole-1-carboxylate (5.5 mg, 16 μmol) and 2-(piperazin-1-yl)pyrimidine (7.9 mg, 48 μmol) in anhydrous DCM (2 mL) was added PL-DIPAM (85 mg, 3.27 mmol/g loading, 315 μmol, Polymer Labs) and the reaction mixture was shaken overnight at room temperature. The resulting mixture was drained into PL-PETA (55 mg, 2.7 mmol/g loading, 175 μmol, Polymer Labs) and PL-MIA, (35 mg, 2.65 mmol/g loading, 104 μmol, Polymer Labs). The reaction mixture was shaken overnight at room temperature, drained and the resin was washed with 3.0 mL of methanol. The combined methanol solution was transferred to a 2 dram vial and concentrated under reduced pressure. The resulting oil was dissolved in methanol (2 mL) followed by the addition of 4 N anhydrous hydrogen chloride in dioxane (0.5 mL, Aldrich). The mixture was shaken at room temperature for an additional 18 hours. The resulting solution was concentrated under reduced pressure to give 7-(2-methyl-1H-benzimidazol-6-yl)-4-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepine. MS (EI) for C26H27N7O2: 470.5 (MH+).

Workup

  1. stirringThe reaction mixture was shaken overnight at room temperature
  2. washthe resin was washed with 3.0 mL of methanol
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting oil was dissolved in methanol (2 mL)
  5. additionfollowed by the addition of 4 N anhydrous hydrogen chloride in dioxane (0.5 mL, Aldrich)
  6. stirringThe mixture was shaken at room temperature for an additional 18 hours
  7. concentrationThe resulting solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b87e7b783c42477e9ed1bd2f2f0f0cd9
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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