Dichloromethane → HCID 49868677, compound

HRID 475015Notes

Reaction equation

HRID 475015 reaction equation
C[CH:2]1[C:8]2[CH2:9][CH2:10][C:11]3[CH2:12][CH:13](C(OC(C)(C)C)=O)[NH:14][C:15]=3[C:7]=2[CH:6]=[N:5][C:4]([N:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:30]=[N:31]C(C(F)(F)F)=[CH:33][CH:34]=3)=[N:25][C:24]2=[O:39])=[CH:3]1.[C:40](O)([C:42]([F:45])([F:44])[F:43])=O.[CH2:47](Cl)[Cl:48]>>[ClH:48].[CH3:47][N:5]1[C:2]2[CH:3]=[C:4]([N:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:30]=[N:31][C:40]([C:42]([F:45])([F:44])[F:43])=[CH:33][CH:34]=4)=[N:25][C:24]3=[O:39])[CH:10]=[CH:9][C:8]=2[C:7]2[CH2:15][NH:14][CH2:13][CH2:12][CH2:11][C:6]1=2

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86762266HCID 86762266, compound

Product 1

HCID 49868677HCID 49868677, compoundYield 37%

Procedure

To a solution of tert-butyl 6-methyl-8-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-1(2H)-yl)-3,4,5,6-tetrahydroazepino[4,3-]indole-2(1H) carboxylate (55 mg, 0.13 mmol) in DCM (10 mL) was added TFA (0.50 mL). The reaction solution was stirred at room temperature for 2 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 resulting free base was converted to the HCl salt using HCl in methanol to afford the title compound (23.0 mg, 37%) as a brown-reddish solid: 1H NMR (500 MHz, CD3OD) δ 9.47 (d, J=1.5 Hz, 1H), 8.80 (dd, J=6.0, 2.0 Hz, 1H), 8.41 (d, J=6.5 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.71 (d, J=8.5 Hz, 1H), 6.64 (d, J=1.5 Hz, 1H), 7.37 (d, J=7.0 Hz, 1H), 7.23 (dd, J=8.5, 2.0 Hz, 1H), 4.58 (s, 2H), 3.72 (s, 3H), 3.61-3.58 (m, 2H), 3.24-3.21 (m, 2H), 2.27-2.20 (m, 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)

Sources & evidence

ORD record
ord-db49402e74e84d4f903e94022f95136c
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

Loading…