1,1'-Carbonyldiimidazole → HCID 86703664, compound

HRID 1849780Notes

Reaction equation

HRID 1849780 reaction equation
[Cl:1][C:2]1[C:3]([CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:32]1([S:36]([NH2:39])(=[O:38])=[O:37])[CH2:35][CH2:34][CH2:33]1.N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C>[N:32]1([S:36]([NH:39][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Cl:1])[C:3]([CH2:12][O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)=[CH:4][C:5]=2[F:11])(=[O:38])=[O:37])[CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 450805661-AzetidinesulfonamideHCID 86703663HCID 86703663, compound

Product 1

HCID 86703664HCID 86703664, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-chloro-4-(cyclohexyloxymethyl)-2-fluorobenzoic acid (0.12 g, 0.42 mmol) in anhydrous tetrahydrofuran (5 mL) was added 1,1′-carbonyldiimidazole (0.088 g, 0.55 mmol). The reaction solution was heated to reflux under a nitrogen atmosphere for 15 minutes and cooled to ambient temperature. To this solution was added azetidine-1-sulfonamide (0.086 g, 63 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 g, 1.05 mmol). The mixture was stirred at ambient temperature for 16 hours, then diluted with ethyl acetate (15 mL) and washed with 1 M hydrochloric acid (2×10 mL) and brine (2×10 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by reverse-phase preparative HPLC to afford the title compound (0.005 g, 3%) as a colorless powder: MS (ES+) m/z 405.1, 407.1 (M+H)

Workup

  1. temperatureThe reaction solution was heated
  2. temperatureto reflux under a nitrogen atmosphere for 15 minutes
  3. washwashed with 1 M hydrochloric acid (2×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to dryness
  7. customThe residue was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-9fb1d76c5adf410db9a73cb914049223
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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