Trifluoroacetic acid → 5-Cyano-1h-imidazole-2-carboxylic acid [4-[4-(2-dimethylamino-ethoxy)-tetrahydro-pyran-4-yl]-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide trifluoroacetic acid salt

HRID 536922Notes

Reaction equation

HRID 536922 reaction equation
[CH3:1][C:2]1([CH3:31])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3([OH:20])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:21][C:22]([C:24]2[NH:25][C:26]([C:29]#[N:30])=[CH:27][N:28]=2)=[O:23])=[CH:4][CH2:3]1.[CH3:32][N:33]([CH3:37])[CH2:34][CH2:35]O.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]>C(Cl)Cl>[F:41][C:40]([F:43])([F:42])[C:38]([OH:44])=[O:39].[CH3:32][N:33]([CH3:37])[CH2:34][CH2:35][O:20][C:14]1([C:12]2[CH:11]=[CH:10][C:9]([NH:21][C:22]([C:24]3[NH:25][C:26]([C:29]#[N:30])=[CH:27][N:28]=3)=[O:23])=[C:8]([C:5]3[CH2:6][CH2:7][C:2]([CH3:31])([CH3:1])[CH2:3][CH:4]=3)[CH:13]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 79022-(Dimethylamino)ethanolHCID 591285735-Cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(4-hydroxy-tetrahydro-pyran-4-yl)-phenyl]-amide

Product 1

HCID 167557405-Cyano-1h-imidazole-2-carboxylic acid [4-[4-(2-dimethylamino-ethoxy)-tetrahydro-pyran-4-yl]-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide trifluoroacetic acid saltYield 20.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 5-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(4-hydroxy-tetrahydro-pyran-4-yl)-phenyl]-amide (48.0 mg, 0.114 mmol)(prepared in Example 1, step (h)) in 1 mL of DCM was added 2-dimethylamino-ethanol (0.114 mL, 1.14 mmol), TFA (0.130 mL, 1.17 mmol), and the mixture heated to 50° C. for 8 h. The mixture was concentrated and the title compound purified by RP-HPLC on a C18 column eluting with a linear gradient of 30-50% CH3CN in 0.1% TFA/H2O over 12 min to give 14 mg (20%) of a white solid. 1H-NMR (400 MHz, CD3OD): δ 8.21 (d, J=8.6 Hz, 1H), 7.91 (s, 1H), 7.35 (dd, J=8.6, 2.2 Hz, 1H), 7.21 (d, J=2.2 Hz, 1H), 5.67 (m, 1H), 3.83-3.66 (m, 4H), 3.30-3.15 (m, 4H), 2.76 (s, 6H), 2.26-2.20 (m, 2H), 2.12-1.94 (m, 6H), 1.51 (t, J=6.3 Hz, 2H), 1.00 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C28H37N5O3, 492.3 (M+H). found 492.0.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe title compound purified by RP-HPLC on a C18 column
  3. washeluting with a linear gradient of 30-50% CH3CN in 0.1% TFA/H2O over 12 min

Sources & evidence

ORD record
ord-7a2a8aeb24314ac6b1b085e81116ab93
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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