Dicyclohexylcarbodiimide → HCID 68388481, compound

HRID 1396036Notes

Reaction equation

HRID 1396036 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]([C:12]1[N:13]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31](S(C)(=O)=O)[C:30]([CH2:37][OH:38])=[C:29]([F:39])[CH:28]=3)=[CH:23][C:22]=2[F:40])[CH:14]=[C:15]([C:17]([OH:20])([CH3:19])[CH3:18])[N:16]=1)([CH3:11])[CH3:10].[C:41]([O:45][P:46]([O:53][CH2:54][C:55]1[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=1)[C:58](O)=[O:59])([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH3:44])([CH3:43])[CH3:42].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:49]([O:48][P:46]([O:53][CH2:54][C:55]1[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=1)[C:58]([O:38][CH2:37][C:30]1[CH:31]=[CH:32][C:27]([C:24]2[CH:25]=[CH:26][C:21]([N:13]3[CH:14]=[C:15]([C:17]([OH:20])([CH3:19])[CH3:18])[N:16]=[C:12]3[C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])([CH3:11])[CH3:10])=[C:22]([F:40])[CH:23]=2)=[CH:28][C:29]=1[F:39])=[O:59])([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:47])([CH3:50])([CH3:51])[CH3:52]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 49787490Bms-852927HCID 683854873-((Di-tert-butoxyphosphoryloxy)methyl)benzoic acid

Product 1

HCID 68388481HCID 68388481, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol (prepared in the manner described in PCT Publication No. WO 2010/138598, 0.1 g, 0.16 mmol) in CH2Cl2 (2 mL) was added 3-((di-tert-butoxyphosphoryloxy)methyl)benzoic acid (140 mg, 0.40 mmol), DMAP (4 mg, 0.33 mmol) and DCC (86 mg, 0.42 mmol). The reaction mixture was stirred at rt. After 15 h, the reaction mixture was filtered, washed with CH2Cl2 (2×10 mL), and the solvents were removed under reduced pressure to yield the crude material. The crude product was purified by column chromatography (basic alumina, EtOAc:Hexane) to afford (4′-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-(2-hydroxypropan-2-yl)-1H-imidazol-1-yl)-3,3′-difluorobiphenyl-4-yl)methyl 3-((di-tert-butoxyphosphoryloxy)methyl)benzoate (95 mg, 0.10 mmol, 62%). LCMS: (Ascentis Express C8 (50×2.1 mm-2.7 μm); Solvent A=10 mM NH4COOH in 98% H2O and 2% acetonitrile; Solvent B=98% acetonitrile and 2% 10 mM NH4COOH in H2O; gradient 0% (1.5 min) then to 100% (1.5-3.2 min), 100% (3.2-4 min) B over 4 min), retention time: 2.22 min; LCMS (MM-ES+APCI), flow 1 mL/min, m/z 937.2.

Workup

  1. filtrationthe reaction mixture was filtered
  2. washwashed with CH2Cl2 (2×10 mL)
  3. customthe solvents were removed under reduced pressure
  4. customto yield the crude material
  5. customThe crude product was purified by column chromatography (basic alumina, EtOAc:Hexane)

Sources & evidence

ORD record
ord-8af70c325f194de3bc5abff255c8d23e
Source dataset
uspto-grants-2014_12
Patent number
US08901106B2

Reaction notes

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