Triethylamine → HCID 178510397, compound

HRID 1991991Notes

Reaction equation

HRID 1991991 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].C1(C2C=C(C3CCNCC3)C=CC=2NC(C2NC=C(C#N)N=2)=O)CCCCC=1.BrCC(OC(C)(C)C)=O.CCN(CC)CC.C([O:56][C:57](=[O:87])[CH2:58][N:59]1[CH2:64][CH2:63][CH:62]([C:65]2[CH:70]=[CH:69][C:68]([NH:71][C:72]([C:74]3[NH:75][CH:76]=[C:77]([C:79]#[N:80])[N:78]=3)=[O:73])=[C:67]([C:81]3[CH2:86][CH2:85][CH2:84][CH2:83][CH:82]=3)[CH:66]=2)[CH2:61][CH2:60]1)(C)(C)C>C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:79]([C:77]1[N:78]=[C:74]([C:72]([NH:71][C:68]2[CH:69]=[CH:70][C:65]([CH:62]3[CH2:61][CH2:60][N:59]([CH2:58][C:57]([OH:87])=[O:56])[CH2:64][CH2:63]3)=[CH:66][C:67]=2[C:81]2[CH2:86][CH2:85][CH2:84][CH2:83][CH:82]=2)=[O:73])[NH:75][CH:76]=1)#[N:80]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 79177tert-Butyl bromoacetateHCID 178451204HCID 178451204, compoundHCID 1785103834-Cyano-1h-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt

Product 1

HCID 178510397HCID 178510397, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A flask was charged with 4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide TFA salt (33 mg, 0.067 mmol) (as prepared in Example 14, step (b)), t-butyl bromoacetate (10 μL, 0.067 mmol), NEt3 (20 μL, 0.135 mmol) and 0.25 mL of DCM and stirred for 10 h at 25° C. The reaction mixture was loaded on a 5 g SPE cartridge (silica) and 23 mg (70%) of (4-{4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-cyclohex-1-enyl-phenyl}-piperidin-1-yl)-acetic acid tert-butyl ester was eluted with 25% EtOAc/DCM. This compound was dissolved in 1 mL of DCM and 20 μL of EtOH and 1 mL of TFA were added and the reaction stirred for 3 h at 25° C. The title compound was purified by RP-HPLC (C18), eluting with 30-50% CH3CN in 0.1% TFA/H2O over 12 min to give 10 mg (40%) of a white solid. 1H-NMR (400 MHz, CD3OD): δ 8.16 (d, 1H), 8.02 (s, 1H), 7.22 (dd, 1H), 7.10 (d, 1H), 5.72 (m, 1H), 4.04. (s, 2H), 3.76 (m, 2H), 3.22 (m, 2H), 2.90 (m, 1H), 2.29 (m, 4H), 2.10 (m, 4H), 1.82 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C24H27N5O3, 434.2 (M+H), found 434.2.

Workup

  1. washwas eluted with 25% EtOAc/DCM
  2. dissolutionThis compound was dissolved in 1 mL of DCM
  3. addition20 μL of EtOH and 1 mL of TFA were added
  4. stirringthe reaction stirred for 3 h at 25° C
  5. customThe title compound was purified by RP-HPLC (C18)
  6. washeluting with 30-50% CH3CN in 0.1% TFA/H2O over 12 min

Sources & evidence

ORD record
ord-1e1a1831991f48c38332a232ee6250dc
Source dataset
uspto-grants-2010_01
Patent number
US07645755B2

Reaction notes

Loading…