Cyclobutylamine → HCID 53234534, compound

HRID 1256124Notes

Reaction equation

HRID 1256124 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:12](=[O:25])(=[O:24])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)=[C:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.[CH:26]1([NH2:30])[CH2:29][CH2:28][CH2:27]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.CO>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:12](=[O:24])(=[O:25])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)=[C:6]([CH2:8][C:9]([NH:30][CH:26]2[CH2:29][CH2:28][CH2:27]2)=[O:11])[CH:7]=1

Participants

7

Reactant 3

HCID 75645CyclobutylamineHCID 2724699PyBOPHCID 53234452HCID 53234452, compound

Product 1

HCID 53234534HCID 53234534, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetic acid (400 mg, 1.2 mmol) and cyclobutylamine (0.8 mL, 6 mmol) in 20 mL of DMF was added PyBOP (850 mg, 1.7 mmol) and TEA (1 mL, 7 mmol). The reaction mixture was stirred for 16 hours. After water was added, the reaction mixture was extracted with ethyl acetate and washed with water, 1N HCl and brine. The organic layer was dried over Na2SO4 and concentrated. The crude residue was purified by ISCO CombiFlash Rf silica chromatography eluted with 88:10:2 chloroform:MeOH:H2O to give the desired product as a yellow solid (250 mg, yield 54%). MS calcd for (C19H22BN3O5S): 415.1. MS found (ESI negative): (M−H)−=414.2. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.85 (s, 1H), 9.17 (s, 1H), 8.28 (d, J=7.6 Hz, 1H), 7.42 (m, 2H), 7.22 (d, J=8.4 Hz, 1H), 7.10 (dd, J=8, 2 Hz, 1H), 6.44 (d, J=2.4 Hz, 1H), 6.34 (dd, J=8, 2 Hz, 1H), 5.93 (bs, 2H), 4.87 (s, 2H), 4.20 (m, 1H), 3.75 (s, 2H), 2.18 (m, 2H), 1.89 (m, 2H), 1.64 (m, 2H).

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washwashed with water, 1N HCl and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude residue was purified by ISCO CombiFlash Rf silica chromatography
  6. washeluted with 88:10:2 chloroform

Sources & evidence

ORD record
ord-147ae4ca16684c2098ea6f675fa68c80
Source dataset
uspto-grants-2013_06
Patent number
US08461134B2

Reaction notes

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