Urea → Boronic Acid

HRID 2092509Notes

Reaction equation

HRID 2092509 reaction equation
CCN(C(C)C)C(C)C.NC(N)=O.[B:14]1(B2OC(C)(C)C(C)(C)O2)[O:18]C(C)(C)C(C)(C)[O:15]1.[CH:32]1[CH:37]=[CH:36][C:35]([P:38]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C-:39]2[CH:43]=[CH:42][CH:41]=[CH:40]2)=[CH:34][CH:33]=1.[CH:50]1[CH:55]=[CH:54][C:53]([P:56]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[C-:57]2[CH:61]=[CH:60][CH:59]=[CH:58]2)=[CH:52][CH:51]=1.[Cl:68][Pd:69][Cl:70].[Fe+2:71]>C(Cl)Cl.C1(C)C=CC=CC=1.O1CCOCC1>[CH:47]1[CH:46]=[CH:45][C:44]([P:38]([C:35]2[CH:36]=[CH:37][CH:32]=[CH:33][CH:34]=2)[C-:39]2[CH:43]=[CH:42][CH:41]=[CH:40]2)=[CH:49][CH:48]=1.[CH:65]1[CH:64]=[CH:63][C:62]([P:56]([C:53]2[CH:54]=[CH:55][CH:50]=[CH:51][CH:52]=2)[C-:57]2[CH:61]=[CH:60][CH:59]=[CH:58]2)=[CH:67][CH:66]=1.[Cl:68][Pd:69][Cl:70].[Fe+2:71].[BH:14]([OH:18])[OH:15]

Participants

9

Reactant 4

HCID 1176UreaHCID 81531DiisopropylethylamineHCID 2733548Bis(pinacolato)diboraneHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)

Product 2

HCID 61668Boronic AcidHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

The fourth route to intermediate [1] is outlined in Scheme 4. Intermediate compound [C] is prepared as described in Scheme 2. 4-Amino benzamide [C] is then reacted with 2,2,2-trichloroethyl chloroformate or trichloromethyl chloroformate to form the corresponding carbamate [P]. Typically, this reaction is performed in the presence of a base such as TEA or DIPEA, solvent such as DCM, THF, or CHCl3, at reduced temperatures, i.e., about 0° C. to about rt, for about 2 to about 12 h, such as about 4 h. Reaction of compound [P] with an appropriately substituted aniline affords urea intermediate [O]. Typically, this reaction is performed in the presence of a base such as TEA or DIPEA, a solvent such as 1,4-dioxane, toluene, or mixtures thereof, at elevated temperatures such as about 90 to about 120° C., i.e., about 95° C., and over a period of about 10 to about 15 h, such as about 10 h. The urea intermediate [O] is then reacted with bis(pinacolato)diboron in the presence of a catalyst such as Pd(dppf)Cl2.DCM or Pd(dppf)Cl2 to form intermediate [1]. Typically, this reaction is performed in the presence of a base such as KOAc, solvent such as 1,4-dioxane or DMF, at elevated temperatures such as about 80 to about 120° C., such as about 110° C., and over a period of about 3 to about 15 h, such as about 10 h.

Sources & evidence

ORD record
ord-b86a79d06e554da2bc800600abfecd72
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Reaction notes

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