Diisopropylethylamine → HCID 178483919, compound

HRID 2367800Notes

Reaction equation

HRID 2367800 reaction equation
FC(F)(F)C(O)=O.[C:8]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH:26][C:27]([C:29]2[NH:30][CH:31]=[C:32]([C:34]#[N:35])[N:33]=2)=[O:28])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1.CCN(C(C)C)C(C)C.Cl.[CH3:46][N:47]([CH2:49][C:50](Cl)=[O:51])[CH3:48]>C(Cl)Cl>[C:8]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:21][CH2:22][N:23]([C:50](=[O:51])[CH2:49][N:47]([CH3:48])[CH3:46])[CH2:24][CH2:25]3)[CH:17]=[CH:16][C:15]=2[NH:26][C:27]([C:29]2[NH:30][CH:31]=[C:32]([C:34]#[N:35])[N:33]=2)=[O:28])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 139949912-(Dimethylamino)acetyl chloride hydrochlorideHCID 1785103834-Cyano-1h-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt

Product 1

HCID 178483919HCID 178483919, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt (as prepared in Example 14, step (b), 655 mg, 1.30 mmol) in DCM (15 mL) was cooled to 0° C. and DIEA (0.92 mL, 5.2 mmol) was added. Dimethylaminoacetyl chloride hydrochloride (211 mg, 1.3 mol) was then added portion wise over 10 min. The reaction mixture was stirred at 0° C. for 30 min and allowed to warm to RT and stirred for 2 h. Solvent was removed in vacuo and the resulting residue was partitioned between brine and DCM. The organic layer was separated, dried (Na2SO4) and concentrated. The residue obtained was purified on silica (5% MeOH: DCM) to obtain 432 mg (70%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 9.49 (s, 1H), 8.24 (d, 1H, J=2.3 Hz), 7.70 (s, 1H), 7.12 (dd, 1H, J=8.4, 2.1 Hz), 7.01 (s, 1H), 5.82 (m, 1H), 4.75 (d, 1H, J=13.4 Hz), 4.13 (d, 1H, J=13.4 Hz), 3.57 (d, 1H, J=14.2 Hz), 3.18 (d, 1H, J=14.2 Hz), 3.12 (td, 1H, J=13.3, 2.4 Hz), 2.73 (dddd, 1H, J=11.9, 11.9, 3.8, 3.8 Hz), 2.65 (ddd, 1H, J=13.3, 13.3, 2.4 Hz), 2.40 (s, 6H), 2.18-2.32 (m, 4H), 1.60-1.98 (m, 8H). Mass spectrum (ESI, m/z): Calcd. for C26H32N6O2, 461.3 (M+H). found 461.2.

Workup

  1. temperatureto warm to RT
  2. stirringstirred for 2 h
  3. customSolvent was removed in vacuo
  4. customthe resulting residue was partitioned between brine and DCM
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue obtained
  9. customwas purified on silica (5% MeOH: DCM)

Sources & evidence

ORD record
ord-345209e72b24426cba5627c67df11c26
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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