1,1'-Carbonyldiimidazole → HCID 66577308, compound

HRID 1529131Notes

Reaction equation

HRID 1529131 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:13]([CH3:35])=[N:14][O:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3([C:32](O)=[O:33])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:48][S:49]([NH2:52])(=[O:51])=[O:50].N12CCCN=C1CCCCC2>C1COCC1.CN(C)C1C=CN=CC=1>[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:13]([CH3:35])=[N:14][O:15][C:16]=1[C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3([C:32]([NH:52][S:49]([CH3:48])(=[O:51])=[O:50])=[O:33])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)=[CH:21][CH:22]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 682631,1'-Carbonyldiimidazole2×HCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 66577397HCID 66577397, compound

Product 1

HCID 66577308HCID 66577308, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

1-{4′-[4-((S)-2-benzyloxy-1-hydroxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (0.232 g, 0.49 mmol) was dissolved in THF (4.6 mL) along with 4-dimethylaminopyridine (0.0065 g, 0.05 mmol) and carbonyldiimidazole (0.200 g, 1.24 mmol). After stirring at room temperature for 3.5 hours, carbonyldiimidazole (0.040 g, 0.25 mmol) was added. The reaction stirred for 1 hour then methanesulfonamide (0.117 g, 1.23 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.242 mL, 1.62 mmol) were added and the reaction was heated to 100° C. After 40 minutes the reaction was cooled and submitted to standard aqueous workup. The residue was purified on silica gel (0-100% EtOAc in hexanes) to afford the a separable mixture of products, of which the minor product was the title compound.

Workup

  1. stirringThe reaction stirred for 1 hour
  2. temperaturethe reaction was heated to 100° C
  3. temperatureAfter 40 minutes the reaction was cooled
  4. customThe residue was purified on silica gel (0-100% EtOAc in hexanes)
  5. customto afford
  6. additionthe a separable mixture of products

Sources & evidence

ORD record
ord-2fa15821b7f84f238280441570803446
Source dataset
uspto-grants-2015_07
Patent number
US09090573B2

Reaction notes

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