Hydrochloric Acid → HCID 66874100, compound

HRID 475002Notes

Reaction equation

HRID 475002 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][CH2:27][N:28](C(OC(C)(C)C)=O)[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][CH2:27][NH:28][CH2:29][CH2:30][C:3]1=2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58093347HCID 58093347, compound

Product 1

HCID 66874100HCID 66874100, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 6-methyl-8-(2-oxo-4-phenethylpyrimidin-1(2H)-yl)-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate (44 mg, 0.088 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 residue was purified by semi-preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.20 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA). 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 the HCl salt using HCl in methanol and lypholized to provide the title compound (19.8 mg, 52%) as a light yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.03 (d, J=7.0 Hz, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.45 (d, J=2.0 Hz, 1H), 7.30-7.28 (m, 4H), 7.22-7.17 (m, 1H), 7.05 (dd, J=8.5, 2.0 Hz, 1H), 6.56 (d, J=6.5 Hz, 1H), 3.73 (s, 3H), 3.42-3.34 (m, 4H), 3.27-3.25 (m, 2H), 3.17-3.15 (m, 2H), 3.10-3.08 (m, 2H), 3.04-3.02 (m, 2H); ESI MS m/z 399 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by semi-preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.20 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA)
  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-6537bbddb72d47fea23a25af3d9e0a36
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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