Nitrogen → HCID 68749804, compound

HRID 390370Notes

Reaction equation

HRID 390370 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[O:33][C:10]3([CH2:15][CH2:14][N:13]([C:16]4[S:17][C:18]([N:21]5[CH:25]=[CH:24][N:23]([CH2:26][C:27]([O:29]CC)=[O:28])[C:22]5=[O:32])=[CH:19][N:20]=4)[CH2:12][CH2:11]3)[CH:9]=2)=[CH:4][CH:3]=1.BrC1SC(N2CCC3(C=C(C4C=CC(F)=CC=4)C4C(=CC=CC=4)O3)CC2)=NC=1.O=C1NC=CN1CC(OCC)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N.CNCCNC.[Al]>O1CCOCC1.C(Cl)Cl.[Cu]I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[O:33][C:10]3([CH2:15][CH2:14][N:13]([C:16]4[S:17][C:18]([N:21]5[CH:25]=[CH:24][N:23]([CH2:26][C:27]([OH:29])=[O:28])[C:22]5=[O:32])=[CH:19][N:20]=4)[CH2:12][CH2:11]3)[CH:9]=2)=[CH:4][CH:3]=1

Participants

11

Reactant 7

HCID 947NitrogenHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 5359268AluminumHCID 59571598HCID 59571598, compoundHCID 66960348HCID 66960348, compoundHCID 68751157HCID 68751157, compound

Product 1

HCID 68749804HCID 68749804, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Step 4 Ethyl 2-(3-(2-(4-(4-fluorophenyl)spiro[chromene-2,4′-piperidine]-1′-yl)thiazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetate A mixture of 1′-(5-bromothiazol-2-yl)-4-(4-fluorophenyl)spiro[chromene-2,4′-piperidine] (93.2 mg, 0.20 mmol), ethyl (2-oxo-2,3-dihydro-1H-imidazol-1-yl)acetate (Example 38, Step 2) (52 mg, 0.31 mmol), copper(I) iodide (39 mg, 0.21 mmol) and K3PO4 (105 mg, 0.49 mmol) was suspended in dry dioxane (2 mL). The reaction mixture was stirred under vacuum for 3 min, then the reaction mixture was backfilled with N2, treated with neat N1,N2-dimethylethane-1,2-diamine (22.9 mg, 0.26 mmol), covered with aluminum foil and stirred in an oil bath preheated at 94° C. for 3.5 h. The reaction mixture was then diluted with DCM (3 mL), washed with saturated NH4Cl (10 mL), 5% KHSO4 (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting oily residue was purified by Combiflash™ chromatography (SiO2 (12 g), eluting with 5-70% EtOAc/hexanes) to afford the title compound as a foam.

Workup

  1. stirringstirred in an oil bath
  2. waitpreheated at 94° C. for 3.5 h
  3. washwashed with saturated NH4Cl (10 mL), 5% KHSO4 (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oily residue was purified by Combiflash™ chromatography (SiO2 (12 g), eluting with 5-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d20d6cd33b9346d9be46f6218d845409
Source dataset
uspto-grants-2013_02
Patent number
US08383643B2

Reaction notes

Loading…