Hydrochloric Acid → 2-Phenylbenzo[d]oxazole-7-carboxamide

HRID 415236Notes

Reaction equation

HRID 415236 reaction equation
[C:1]1([C:7]2[O:8][C:9]3[C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=[N:25]C=2C=1.[NH4+].[Cl-].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[C:1]1([C:7]2[O:8][C:9]3[C:15]([C:16]([NH2:25])=[O:18])=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 118067277-Benzoxazolecarboxylic acid, 2-phenyl-

Product 1

HCID 666208062-Phenylbenzo[d]oxazole-7-carboxamideYield 16%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-phenylbenzo[d]oxazole-7-carboxylic acid in DMF (15 mL) was added HOBt (148 mg, 1.1 mmol), NH4Cl (54 mg, 1.0 mmol), DIPEA (387 mg, 3.0 mmol) and EDCI (211 mg, 1.1 mmol). The mixture was stirred at 25° C. for 10 hr. To the resulting mixture, water (10 mL) and aqueous hydrochloric acid (1 N) was added to pH=3, then extracted with ethyl acetate (100 mL×4). The organic phase was washed with saturated sodium bicarbonate solution and brine, concentrated and dried in vacuum. The crude product was purified by pre-HPLC to obtain 2-phenylbenzo[d]oxazole-7-carboxamide as a white solid (40 mg, yield 16% for 2 steps). 1H-NMR (400 MHz, DMSO-d6) δ 7.48-7.52 (t, J=8 Hz, 1H), 7.62-7.68 (m, 3H), 7.81-7.83 (dd, J1=8 Hz, J2=1 Hz, 1H), 7.88-7.92 (d, J=8 Hz, 2H), 7.96-7.99 (dd, J1=8 Hz, J2=1 Hz, 1H), 8.30-8.33 (dd, J1=8 Hz, J2=2 Hz, 2H); LC-MS (ESI) m/z 239 [M+1]+.

Workup

  1. extractionextracted with ethyl acetate (100 mL×4)
  2. washThe organic phase was washed with saturated sodium bicarbonate solution and brine
  3. concentrationconcentrated
  4. customdried in vacuum
  5. customThe crude product was purified by pre-HPLC

Sources & evidence

ORD record
ord-05a97340bda84ec6bf0d644fa49871fd
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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