Isopropanol → 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid isopropyl ester

HRID 1877949Notes

Reaction equation

HRID 1877949 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:17]([OH:19])=[O:18])[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[CH2:11][CH2:10]2)=[C:5]([F:20])[CH:4]=1)#[N:2].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH3:32][CH:33](O)[CH3:34]>C(Cl)Cl.CCN(CC)CC>[CH:33]([O:18][C:17]([C:9]1([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[F:20])[N:13]2[CH:14]=[N:15][CH:16]=[C:12]2[CH2:11][CH2:10]1)=[O:19])([CH3:34])[CH3:32]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 58827042HCID 58827042, compound

Product 1

HCID 588270595-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

5-(4-Cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid (0.15 g, 0.279 mmol) is suspended in CH2Cl2 (3 mL) and DMF (0.01 ml) and cooled to 0° C. A solution of oxalyl chloride (0.31 mL, 2 M) in CH2Cl2 is added dropwise. After 1 h i-PrOH (3 mL) is added. After 2 h Et3N is added until basic and the solution is concentrated. The resulting slurry is dissolved in CH2Cl2, washed with aqueous saturated NaHCO3/H2O (1:1) and brine, then dried over Na2SO4. After concentration, the residue is purified by HPLC (2-38% MeCN/H2O containing 0.1% TFA) to give 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid isopropyl ester as solid. MS (ESI) m/z 314.0 (M+H); 1H NMR (400 MHz, CD3CN) (TFA salt) δ ppm 1.22 (d, J=6.06 Hz, 3 H), 1.23 (d, J=6.06 Hz, 3 H), 3.01-3.18 (m, 3 H), 3.38-3.45 (m, 1 H), 5.08-5.18 (m, 1 H), 7.20 (s, 1 H), 7.34 (app t, J=8.08 Hz, 1 H), 7.62-7.68 (m, 2 H) 8.52 (s, 1 H).

Workup

  1. concentrationis concentrated
  2. dissolutionThe resulting slurry is dissolved in CH2Cl2
  3. washwashed with aqueous saturated NaHCO3/H2O (1:1) and brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentration
  6. customthe residue is purified by HPLC (2-38% MeCN/H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-669db39fdf794120a679ffeb0003ced1
Source dataset
uspto-grants-2012_11
Patent number
US08314097B2

Reaction notes

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