3-Aminobenzamide → HCID 67444082, compound

HRID 1400824Notes

Reaction equation

HRID 1400824 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]5[CH2:27][CH2:26][CH2:25][C:24]5=[O:28])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1.CCN(C(C)C)C(C)C.ClC(Cl)(O[C:45](=[O:51])OC(Cl)(Cl)Cl)Cl.[NH2:53][C:54]1[CH:55]=[C:56]([CH:60]=[CH:61][CH:62]=1)[C:57]([NH2:59])=[O:58]>C1COCC1>[F:31][C:4]1[CH:3]=[C:2]([NH:1][C:45](=[O:51])[NH:53][C:54]2[CH:55]=[C:56]([CH:60]=[CH:61][CH:62]=2)[C:57]([NH2:59])=[O:58])[CH:30]=[CH:29][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][C:24]4=[O:28])=[CH:20][N:21]=3)[S:15][C:8]=12

Participants

6

Reactant 4

HCID 16453-AminobenzamideHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 58474708HCID 58474708, compound

Product 1

HCID 67444082HCID 67444082, compoundYield 7.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 104 (83 mg, 0.191 mmol, scheme 26) in THF (19 mL) at −10° C. was added DIPEA (334 μl, 1.910 mmol) and triphosgene (56.7 mg, 0.191 mmol). The reaction mixture was stirred for 90 min at −10° C. then 3-aminobenzamide (104 mg, 0.764 mmol) was added. The reaction mixture was allowed to warm to RT, stirred for 3 h, quenched with MeOH, and concentrated. The residue was suspended in 2 mL of MeOH and a saturated aqueous solution of ammonium chloride was added, stirred for 30 min, collected by filtration, and dried. The crude product was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 30/70 over 20 CV) to produce a material that was further purified by Gilson (Phenomenex, Luna, 15μ, C18(2) 100A, 250×50.00 mm, 15 μm, 0.05% of formic acid in both MeOH/water (30 mL/min): 30/70 to 95/5 over 60 min), to afford the title compound 106 (8.7 mg, 0.015 mmol, 7% yield, formate salt) as an yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 11.34 (s, 1H), 11.06 (s, 1H), 8.55-8.50 (m, 2H), 8.41 (s, 4H), 8.35 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 8.05 (t, J=2.0 Hz, 1H), 7.90-7.77 (m, 3H), 7.71-7.67 (m, 1H), 7.44-7.38 (m, 3H), 7.34-7.27 (m, 2H), 6.68 (dd, J=5.2, 0.8 Hz, 1H), 4.46 (s, 2H), 3.31 (t, J=7.2 Hz, 2H), 2.31 (t, J=8.0 Hz, 2H), 1.95 (quint, J=8.0 Hz, 2H). MS (m/z): 597.5 (M+H).

Workup

  1. temperatureto warm to RT
  2. stirringstirred for 3 h
  3. customquenched with MeOH
  4. concentrationconcentrated
  5. additiona saturated aqueous solution of ammonium chloride was added
  6. stirringstirred for 30 min
  7. filtrationcollected by filtration
  8. customdried
  9. customThe crude product was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 30/70 over 20 CV)
  10. customto produce a material that
  11. customwas further purified by Gilson (Phenomenex, Luna, 15μ, C18(2) 100A, 250×50.00 mm, 15 μm, 0.05% of formic acid in both MeOH/water (30 mL/min)

Sources & evidence

ORD record
ord-6ba29ad33ceb4c99b9ef9c4178339a62
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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