Hydrochloric Acid → HCID 66874864, compound

HRID 474952Notes

Reaction equation

HRID 474952 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:18]=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=4)=[N:13][C:12]3=[O:27])[CH:7]=[CH:6][C:5]=2[C:4]2[CH2:28][CH2:29][N:30](C(OC(C)(C)C)=O)[CH2:31][CH2:32][C:3]1=2.[ClH:40]>ClCCl>[ClH:40].[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:18]=[N:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=4)=[N:13][C:12]3=[O:27])[CH:7]=[CH:6][C:5]=2[C:4]2[CH2:28][CH2:29][NH:30][CH2:31][CH2:32][C:3]1=2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66873656HCID 66873656, compound

Product 1

HCID 66874864HCID 66874864, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 6-methyl-8-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-1(2H)-yl)-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (36 mg, 0.067 mmol) in dichloromethane (1.0 mL) was added HCl (2M in diethyl ether, 5.0 mL). The resulting slurry was stirred at room temperature for 14 h and then concentrated under reduced pressure. The resulting 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, concentrated under reduced pressure and lypholized overnight. The trifluroacetate salt was dissolved in a 1:2 mixture of acetonitrile and water (10 mL) and passed through a plug of SAX column. The column was further washed with a 1:2 mixture of acetonitrile and water (10 mL). The combined filtrate was lypholized to give the title compound (30.1 mg, 94%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.48 (s, 1H), 8.80 (d, J=8.5 Hz, 1H), 8.38 (d, J=6.5 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.59 (d, J=1.0 Hz, 1H), 7.36 (d, J=7.0 Hz, 1H), 7.18 (dd, J=8.5, 1.5 Hz, 1H), 3.78 (s, 3H), 3.56 (t, J=5.5 Hz, 2H), 3.50 (t, J=5.5 Hz, 2H), 3.37 (t, J=5.5 Hz, 2H), 3.26 (t, J=5.5 Hz, 2H); ESI MS m/z 440 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting 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. waitlypholized overnight
  5. dissolutionThe trifluroacetate salt was dissolved in a 1:2 mixture of acetonitrile and water (10 mL)
  6. washThe column was further washed with a 1:2 mixture of acetonitrile and water (10 mL)

Sources & evidence

ORD record
ord-734bbabbd91a43f7a7d16b10dba92676
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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