Triethylamine → HCID 66833261, compound

HRID 579568Notes

Reaction equation

HRID 579568 reaction equation
Cl.Cl.[NH2:3][C:4]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)([CH2:8][CH2:9][CH2:10][CH2:11][B:12]([OH:14])[OH:13])[C:5]([OH:7])=[O:6].C(N(CC)CC)C.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][N:36]=[C:37]=[O:38])=[CH:31][CH:30]=1>CN(C=O)C.Cl>[ClH:28].[NH2:3][C:4]([CH:15]1[CH2:16][CH2:17][N:18]([C:37](=[O:38])[NH:36][CH2:35][C:32]2[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=2)[CH2:19][CH2:20]1)([CH2:8][CH2:9][CH2:10][CH2:11][B:12]([OH:14])[OH:13])[C:5]([OH:7])=[O:6]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 33723791-Chloro-4-(isocyanatomethyl)benzeneHCID 66833181HCID 66833181, compound

Product 1

HCID 66833261HCID 66833261, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred solution of crude 2-amino-6-borono-2-(piperidin-4-yl)hexanoic acid dihydrochloride (Example 26-A, Step 1, 0.240 g, 0.594 mmol) in dry DMF (12 mL) under nitrogen was treated with triethylamine (0.662 mL, 4.75 mmol) to give a white slurry. 1-chloro-4-(isocyanatomethyl)benzene (0.177 mL, 1.34 mmol) was added dropwise, and the resulting opaque mixture was stirred at room temperature for 1 h. The mixture was diluted with 1 N HCl (15 mL) and washed with ethyl acetate (2×20 mL), and the aqueous layer was concentrated under reduced pressure to give the crude product which was purified by reverse phase HPLC [Phenomenex Luna 250×30.00 mm, 10 micron column. 40 mL/min flow rate. Gradient: solvent A is 0.07% TFA in acetonitrile; solvent B is 0.10% TFA in water; 5% to 50% A over 24 min, then 50% to 100% A over 1 min]. Product fractions were pooled and concentrated, and the residue was taken up in 0.5N HCl (5 mL)/acetonitrile (8 mL) and concentrated. The residue was once again treated with 0.5N HCl (5 mL)/acetonitrile (8 mL) and concentrated and dried under high vacuum overnight to give 2-amino-6-borono-2-{1-[(4-chlorobenzyl)carbamoyl]-piperidin-4-yl}hexanoic acid hydrochloride (92 mg, 34%) as an off-white solid. 1H NMR (D2O, 400 MHz) δ 7.26 (m, 2H), 7.15 (m, 2H), 4.19 (s, 2H), 3.95 (bt, J=14.6 Hz, 2H), 2.75 (bt, J=12.8 Hz, 2H), 2.06 (bt, J=12.4 Hz, 1H), 1.81 (m, 3H), 1.53 (bd, J=12.8 Hz, 1H), 1.32 (m, 4H), 1.11 (m, 2H), 0.69 (t, J=7.6 Hz, 2H). ESI+ MS found for C19H29BClN3O5 m/z 408.4 (M−18+H); ESI− MS m/z 424.4 (M−H), 406.4 (M−18−H).

Workup

  1. customto give a white slurry
  2. washwashed with ethyl acetate (2×20 mL)
  3. concentrationthe aqueous layer was concentrated under reduced pressure
  4. customto give the crude product which
  5. customwas purified by reverse phase HPLC [Phenomenex Luna 250×30.00 mm, 10 micron column
  6. wait5% to 50% A over 24 min
  7. wait50% to 100% A over 1 min]
  8. concentrationconcentrated
  9. concentrationconcentrated
  10. additionThe residue was once again treated with 0.5N HCl (5 mL)/acetonitrile (8 mL)
  11. concentrationconcentrated
  12. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-a4475aff038f4b01a9ff88e5c0c3255a
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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