Diisopropylethylamine → HCID 89781888, compound
Reaction equation
[NH2:1][C:2]1[C:10]([Br:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC.Cl.[O:31]1[CH2:36][CH2:35][CH:34]([NH2:37])[CH2:33][CH2:32]1.CCN(C(C)C)C(C)C>CCOC(C)=O>[NH2:1][C:2]1[C:10]([Br:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:37][CH:34]1[CH2:35][CH2:36][O:31][CH2:32][CH2:33]1)=[O:6]Participants
Conditions
- Temperature
- 0 °C
Procedure
A yellow mixture of 2-amino-3-bromobenzoic acid (Oakwood Products, Inc., West Columbia, S.C., 2.125 g, 9.83 mmol), 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (6.37 mL, 10.82 mmol), tetrahydro-2H-pyran-4-amine hydrochloride (Combi-Blocks, Inc., San Diego, Calif., 4.06 g, 29.5 mmol), and DIEA (5.15 mL, 29.5 mmol) was stirred at 0° C. for 5 min; the reaction mixture was then warmed to RT and stir for 30 min when product was observed via LCMS. The reaction mixture was diluted with EtOAc (150 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (4×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated to give 2-amino-3-bromo-N-(tetrahydro-2H-pyran-4-yl)benzamide (515a, 1.54 g, 5.15 mmol, 52% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.49-1.63 (m, 2H) 2.00 (dd, J=12.52, 2.15 Hz, 2H) 3.53 (td, J=11.69, 2.05 Hz, 2H) 3.95-4.05 (m, 2H) 4.10-4.21 (m, 1H) 5.87 (d, J=7.24 Hz, 1H) 6.06 (br. s., 2H) 6.54 (t, J=7.92 Hz, 1H) 7.25-7.30 (m, 1H) 7.51 (dd, J=7.82, 1.17 Hz, 1H). MS (ESI, pos. ion) m/z: 299.0/301.0 (M+1).
Workup
- temperaturethe reaction mixture was then warmed to RT
- stirringstir for 30 min when product
- additionadded to a separatory funnel
- washwashed with saturated aqueous NaHCO3 (4×100 mL)
- customthe organic layer was separated
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-9b2950b4e7114b748fb881cc6335079b
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394297B2
Reaction notes
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