Hydrochloric Acid → 1-(6-Methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-phenethylpyrimidin-2 (1H)-one hydrochloride

HRID 475013Notes

Reaction equation

HRID 475013 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:13][C:12]3=[O:25])[CH:7]=[CH:6][C:5]=2[C:4]2[CH2:26][N:27](C(OC(C)(C)C)=O)[CH2:28][CH2:29][CH2:30][C:3]1=2.[ClH:38]>ClCCl>[ClH:38].[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:13][C:12]3=[O:25])[CH:7]=[CH:6][C:5]=2[C:4]2[CH2:26][NH:27][CH2:28][CH2:29][CH2:30][C:3]1=2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66873854tert-butyl 6-methyl-8-(2-oxo-4-phenethylpyrimidin-1(2H)-yl)-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate

Product 1

HCID 668867311-(6-Methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)-4-phenethylpyrimidin-2 (1H)-one hydrochlorideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 6-methyl-8-(2-oxo-4-phenethylpyrimidin-1(2H)-yl)-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate (25 mg, 0.068 mmol) in dichloromethane (4.0 mL) was added HCl (2M in diethyl ether, 4.0 mL). The resulting slurry was stirred at room temperature for 2 days and then concentrated under reduced pressure. The resulting residue was purified by semi-preparative HPLC. The clean fractions were combined and concentrated under reduced pressure. The resulting trifluoroacetate salt was treated with aqueous sodium carbonate and extracted with EtOAc (2×). The combined organic extract was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The free base was converted to its HCl salt using HCl in methanol and lypholized to provide the title compound (18.0 mg, 60%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.17 (d, J=6.5 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.55 (d, J=2.0 Hz, 1H), 7.32-7.26 (m, 4H), 7.22-7.18 (m, 1H), 7.15 (dd, J=8.5, 2.0 Hz, 1H), 6.64 (d, J=6.5 Hz, 1H), 4.56 (s, 2H), 3.79 (s, 3H), 3.60-3.57 (m, 2H), 3.27-3.20 (m, 2H), 3.14-3.06 (m, 4H), 2.23-2.18 (m, 2H); ESI MS m/z 399 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting residue was purified by semi-preparative HPLC
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting trifluoroacetate salt was treated with aqueous sodium carbonate
  5. extractionextracted with EtOAc (2×)
  6. extractionThe combined organic extract
  7. washwas washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b2bd82c55a134eddb90c8eb8bc807cd3
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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