1,1'-Carbonyldiimidazole → HCID 53357172, compound

HRID 410019Notes

Reaction equation

HRID 410019 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:25])[C:7]([C:16]3[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].C1CCN2C(=NCCC2)CC1>C1COCC1>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:25])[C:7]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])=[O:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5426788HCID 5426788, compound

Product 1

HCID 53357172HCID 53357172, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzoic acid (synthesis is described in PCT/US2010/024035) (100 mg, 0.28 mmol) in THF (10 ml) was added CDI (139 mg, 0.86 mmol) at room temperature. The mixture was stirred for 2 hours. MeSO2NH2 (280 mg, 2.86 mmol) was added in one portion, followed by DBU (394 mg, 2.86 mmol). The mixture was stirred for 4 hours and partitioned between 1N HCl (30 ml) and ethyl acetate (100 ml). The organic phase was separated, washed with brine (50 ml), dried over Na2SO4 and concentrated to give the desired product contaminated with the acid starting material. The mixture was difficult to purify and the acid contaminant was converted into the methyl ester by treatment with SOCl2 (91 mg, 0.77 mmol) in MeOH (4 ml) at 0° C. When the addition was complete, the mixture was stirred for 3 days. The volatiles were removed under reduced pressure and the residue was purified by prep-HPLC to afford the desired product in Example 10 as a white powder (25 mg, 20.5%).

Workup

  1. stirringThe mixture was stirred for 4 hours
  2. custompartitioned between 1N HCl (30 ml) and ethyl acetate (100 ml)
  3. customThe organic phase was separated
  4. washwashed with brine (50 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-984bd8b284444525913ffe3eceddfa2d
Source dataset
uspto-grants-2014_06
Patent number
US08759548B2

Reaction notes

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