2-Methoxyethylamine → HCID 178495853, compound

HRID 536924Notes

Reaction equation

HRID 536924 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(O)[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.O=S(Cl)Cl.[CH3:36][O:37][CH2:38][CH2:39][NH2:40]>C(Cl)Cl.CCOC(C)=O>[CH3:31][C:2]1([CH3:1])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3([NH:40][CH2:39][CH2:38][O:37][CH3:36])[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:28][CH:27]=[C:26]([C:29]#[N:30])[N:25]=2)=[O:23])=[CH:4][CH2:3]1

Participants

6

Reactant 3

HCID 80182-MethoxyethylamineHCID 24386Thionyl ChlorideHCID 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 178495853HCID 178495853, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(4-hydroxy-tetrahydro-pyran-4-yl)-phenyl]-amide (as prepared in Example 1, step (h), 50.0 mg, 0.120 mmol) in 1.5 mL of DCM at 0° C. was added SOCl2 (26.0 μL, 0.360 mmol) under Ar. After stirring at RT for 2 h, the mixture was cooled to 0° C. To the reaction was then added 2-methoxyethylamine (104 μL, 1.20 mmol) and the resulting mixture was stirred at 0° C. for 2 h. The mixture was diluted with EtOAc (30 mL) and washed with H2O (2×10 mL) and brine (10 mL). After drying over Na2SO4 and concentrating in vacuo, the residue was purified by silica gel chromatography (1-4% MeOH/DCM) to afford the title compound (36.8 mg, 65%) as a white solid. 1H-NMR (1:5 CD3OD/CDCl3; 400 MHz): δ 8.31 (d, 1H, J=8.6 Hz), 7.70 (s, 1H), 7.30 (dd, 1H, J=8.6, 2.3 Hz), 7.20 (d, 1H, J=2.3 Hz), 5.77 (m, 1H), 3.94 (m, 2H), 3.69 (m, 2H), 3.41 (t, 2H, J=6.1 Hz), 3.28 (s, 3H), 2.38 (t, 2H, J=6.1 Hz), 2.28 (m, 2H), 2.07-2.20 (m, 4H), 1.88 (m, 2H), 1.59 (t, 2H, J=6.3 Hz), 1.10 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H35N5O3, 476.3 (M−H). found 476.3.

Workup

  1. temperaturethe mixture was cooled to 0° C
  2. washwashed with H2O (2×10 mL) and brine (10 mL)
  3. dry with materialAfter drying over Na2SO4
  4. concentrationconcentrating in vacuo
  5. customthe residue was purified by silica gel chromatography (1-4% MeOH/DCM)

Sources & evidence

ORD record
ord-521000a277624476be2b48d1340904b0
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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