Salicylic Acid → 3-Hydroxybenzamide

HRID 906639Notes

Reaction equation

HRID 906639 reaction equation
C(N(CC=C)CC1SC(S(N2CCC(NC3C=CC=C(S(C(F)(F)F)(=O)=O)C=3)CC2)(=O)=O)=CC=1)C=C.C[N:38]1[C:45](=[O:46])[CH2:44][C:42](=O)N(C)C1=O.[C:48](O)(=O)[C:49]1[C:50](=[CH:52]C=CC=1)[OH:51].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:51][C:50]1[CH:52]=[C:44]([CH:42]=[CH:48][CH:49]=1)[C:45]([NH2:38])=[O:46]

Participants

8

Reactant 5

HCID 338Salicylic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69860Dimethylbarbituric acidHCID 757711-HydroxybenzotriazoleHCID 86761398N,N-Diallyl-N-({5-[(4-{3-[(trifluoromethyl)sulfonyl]anilino}piperidin-1-yl)sulfonyl]-thien-2-yl}methyl)amine

Product 1

HCID 3424033-Hydroxybenzamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

A solution of the bisallylamine 269c (1.15 g, 2.04 mmol), N,N′-dimethylbarbituric acid (NDMBA, 637 mg, 4.08 mmol), and Pd(PPh3)4 (110 mg, 0.096 mmol) in CH2Cl2 (20 mL) was degassed by bubbling argon for 10 min. The reaction was stirred at 23° C. over the week-end (3 d), concentrated, diluted with DMF (12 mL), and treated with salicylic acid (290 mg, 2.10 mmol), 1-hydroxybenzotriazole (HOBt, 283 mg, 2.10 mmol), and N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide (EDC, 402 mg, 2.10 mmol) for 24 h at 23° C. Dilution with EtOAc, washing (H2O, NaHCO3 sat., brine), drying (MgSO4), and evaporation afforded the crude 3-hydroxybenzamide. Purification by reverse-phase prep. HPLC (C8, H2O:CH3CN 60:40→0:100 over 40 min, r.t=23 min) and freeze-drying afforded 466 mg (38% from 269c) of the title 3-hydroxybenzamide as a white powder: NMR (DMSO-d6) δ 12.1 (s, 1H), 9.48 (t, J=5.9 Hz, 1H), 7.86 (dd, 7.9, 1.5 Hz, 1H), 7.50 (d, J=3.8 Hz, 1H), 7.45 (t, J=8.1 Hz, 1H), 7.41 (dd, J=8.9, 1.5 Hz, 1H), 7.21 (d, J=3.8 Hz, 1H), 7.18-7.10 (m, 3H), 6.93 (d, J=83 Hz, 1H), 6.91 (td, J=8.4, 1.1 Hz, 1H), 6.52 (d, J=7.7 Hz, 1H), 4.73 (d, J=5.8 Hz, 2H), 3.57-3.47 (br. d, 12.1, 2H), 3.52-3.35 (br. m., 1H), 2.62 (t, J=10.4 Hz, 2H), 2.07 (s, 1.2H, residual CH3CN), 2.02-1.92 (br. d, J=10.4 Hz, 2H), 1.47 (qd, 11.2, 3.6 Hz, 2H). 13C NMR (DMSO-d6) δ167.52 (s, C═O), 158.36 (s), 148.98 (s), 147.85 (s), 132.83 (d), 132.74 (s), 131.47 (d), 130.00 (d), 128.98 (s), 127.09 (d), 125.52 (d), 124.83 (s), 118.92 (q, residual CH3CN), 11834 (q, J=326 Hz, CF3), 117.75 (d), 116.24 (d), 115.23 (d), 114.19 (q), 111.33 (d), 45.93 (d), 43.66 (t), 36.66 (t), 29.18 (t), 0.00 (s, residual CH3CN). M/Z APCI: 604 (M+1), 602 (M−1). Anal. HPLC: R.t=6.60 min (method a). C24H24F3N3O6S3. 0.3 CH3CN 1.0 H2O Calc.: C, 47.53%. H, 4.36%. N, 7.44%. Found: C, 47.41%, H, 4.09%, N, 7.49%.

Workup

  1. customby bubbling argon for 10 min
  2. concentrationconcentrated
  3. additiondiluted with DMF (12 mL)
  4. washDilution with EtOAc, washing (H2O, NaHCO3 sat., brine)
  5. customdrying
  6. custom(MgSO4), and evaporation

Sources & evidence

ORD record
ord-efb97f77b6fc483aada378c62e54b5bf
Source dataset
uspto-grants-2011_09
Patent number
US08012995B1

Reaction notes

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