Ethyl bromoacetate → HCID 68862385, compound

HRID 536925Notes

Reaction equation

HRID 536925 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][C:9]1([CH3:43])[CH2:14][CH2:13][C:12]([C:15]2[CH:20]=[C:19]([C:21]3([N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:33][C:34]([C:36]2[NH:37][C:38]([C:41]#[N:42])=[CH:39][N:40]=2)=[O:35])=[CH:11][CH2:10]1.CCN(CC)CC.Br[CH2:52][C:53]([O:55]CC)=[O:54].[OH-].[K+]>C(Cl)Cl.O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:41]([C:38]1[NH:37][C:36]([C:34]([NH:33][C:16]2[CH:17]=[CH:18][C:19]([C:21]3([N:27]4[CH2:32][CH2:31][N:30]([CH2:52][C:53]([OH:55])=[O:54])[CH2:29][CH2:28]4)[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)=[CH:20][C:15]=2[C:12]2[CH2:13][CH2:14][C:9]([CH3:43])([CH3:8])[CH2:10][CH:11]=2)=[O:35])=[N:40][CH:39]=1)#[N:42]

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 86616012HCID 86616012, compound

Product 1

HCID 68862385HCID 68862385, compoundYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(4-piperazin-1-yl-tetrahydro-pyran-4-yl)-phenyl]-amide trifluoroacetic acid salt (22 mg, 0.036 mmol) (prepared in Example 1, step (h)) in DCM (0.3 mL) was added NEt3 (0.015 mL, 0.11 mmol) and ethyl bromoacetate (0.0044 mL, 0.040 mmol) and the mixture stirred for 10 h at RT. The mixture was concentrated and the residue dissolved in 1 mL of EtOH and 7N KOH (0.031 mL, 0.22 mmol) was added and the mixture stirred for 3 h at RT. The mixture was diluted with 5 mL of H2O, the pH adjusted to 2, and the title compound purified by RP-HPLC on a C18 column eluting with a linear gradient of 20-50% CH3CN in 01% TFA/H2O over 10 min to give 22 mg (91%) of a white solid. 1H-NMR (400 MHz, CD3OD): δ 8.41 (d, J=8.6 Hz, 1H), 8.01 (s, 1H), 7.44 (dd, J=8.6, 2.2 Hz, 1H), 7.31 (d, J=2.2 Hz, 1H), 5.81 (m, 1H), 4.00-3.92 (m, 2H), 3.70 (s, 2H), 3.42-3.34 (m, 2H), 3.26-2.86 (m, 8H), 2.70-2.58 (m, 2H), 2.38-2.29 (m, 2H), 2.23-2.05 (m, 4H), 1.60 (t, J=6.3 Hz, 2H), 1.10 (s, 6H). Mass spectrum (APCI, m/z): Calcd. for C30H38N6O4, 545.3 (M−H). found 545.3.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue dissolved in 1 mL of EtOH
  3. stirringthe mixture stirred for 3 h at RT
  4. customthe title compound purified by RP-HPLC on a C18 column
  5. washeluting with a linear gradient of 20-50% CH3CN in 01% TFA/H2O over 10 min

Sources & evidence

ORD record
ord-da0e635d5f5d435396d78b44684cf9f1
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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