2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → HCID 71599372, compound

HRID 1622447Notes

Reaction equation

HRID 1622447 reaction equation
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=3[CH3:20])[C:6]=2[CH:5]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:3]=1.C([O:30][B:31]1OC(C)(C)C(C)(C)[O:32]1)(C)C>>[Cl:19][C:15]1[C:14]([CH3:20])=[C:13]([CH2:12][N:7]2[C:6]3[CH:5]=[C:4]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH:3]=[C:2]([B:31]([OH:32])[OH:30])[C:10]=3[N:9]=[C:8]2[CH3:11])[CH:18]=[CH:17][CH:16]=1

Participants

3

Reactant 2

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 71599638HCID 71599638, compound

Product 1

HCID 71599372HCID 71599372, compoundYield 23.4%

Procedure

Several batches were prepared, using additional 77 g of 4-bromo-1-[(3-chloro-2-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole (177.11 mmol), either by the method above or by using 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as the quenching agent. After standard work up the batches were combined with the above material and purified first by RP-HPLC (Luna C18(2), 5 u, 101×250 mm, 55:45 300 mM Aqueous ammonium trifluoroacetate (pH 2.8):acetonitrile), followed by purification on chiral phase (Chiralpak AD 101×250 mm, 20 u, 80:20 Heptane/EtOH plus 2% HCO2H and 1% Isopropylamine) and recrystallization from EtOAc to give [1-[(3-chloro-2-methylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazol-4-yl]boronic acid (18.03 g, 45.17 mmol, 23.4% yield) as a beige powder.

Workup

  1. customSeveral batches were prepared
  2. custompurified first by RP-HPLC (Luna C18(2), 5 u, 101×250 mm, 55:45 300 mM Aqueous ammonium trifluoroacetate (pH 2.8):acetonitrile)
  3. customfollowed by purification on chiral phase (Chiralpak AD 101×250 mm, 20 u, 80:20 Heptane/EtOH plus 2% HCO2H and 1% Isopropylamine) and recrystallization from EtOAc

Sources & evidence

ORD record
ord-8319301a605b4d7db0273c3d1081ee2e
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

Loading…