Diisopropylethylamine → HCID 69745144, compound

HRID 1062424Notes

Reaction equation

HRID 1062424 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:11]=[C:12]([C:14](O)=[O:15])[N:13]=1.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:50][C@@H:51]1[CH2:56][CH2:55][CH2:54][CH2:53][C@H:52]1[OH:57]>ClCCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:11]=[C:12]([C:14]([NH:50][C@@H:51]2[CH2:56][CH2:55][CH2:54][CH2:53][C@H:52]2[OH:57])=[O:15])[N:13]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 22285590HCID 22285590, compound

Product 1

HCID 69745144HCID 69745144, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

In a 20-mL screw-cap vial, 182 mg (0.5 mmol) 2-(2,4-dichlorophenyl)-1-(4-methoxyphenyl)-1H-imidazole-4-carboxylic acid, 145 mg (0.55 mmol) TFFH, and 5.0 equiv. PS-DIEA (loading level: 3.50 mmol/g, 716 mg, 2.5 mmol) were heated in 10 mL 1,2-dichloroethane at 35° C. overnight. The formation of acyl fluoride was monitored by LC-MS. To the mixture, 1.1 equiv. (84 mg, 0.55 mmol) trans-2-aminocyclohexanol hydrochloride was added and the reaction continued overnight. The mixture was filtered through a filter tube (polypropylene frit), and the filtrate was evaporated under reduced pressure. The crude product was redissolved in 1 mL MeOH and purified by preparative HPLC to give 53 mg of 2-(2,4-dichlorophenyl)-N-(trans-2-hydroxycyclohexyl)-1-(4-methoxyphenyl)-1H-imidazole-4-carboxamide (amber oil, 23% yield). 1H NMR (400 MHz, CD2Cl2) δ 7.90 (s, 1 H), 7.30-7.50 (m, 4 H), 7.10 (d, 2 H), 6.90 (d, 2 H), 3.85 (s, 3 H), 3.80 (m, 1 H), 3.50 (m, 1 H), 3.25 (bs, 1 H), 2.0 (m, 2 H), 1.75 (m, 2 H), 1.30-1.50 (m, 4 H); LC-MS m/z 460.2 (MH+), retention time 3.31 min (method 2).

Workup

  1. customIn a 20-mL screw-cap vial
  2. customthe reaction continued overnight
  3. filtrationThe mixture was filtered through a filter tube (polypropylene frit)
  4. customthe filtrate was evaporated under reduced pressure
  5. dissolutionThe crude product was redissolved in 1 mL MeOH
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-9e850cd87cfd4c6d995f6e37b9c097bd
Source dataset
uspto-grants-2005_11
Patent number
US06960601B2

Reaction notes

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