Benzylamine → HCID 68278257, compound

HRID 931458Notes

Reaction equation

HRID 931458 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[N:13]=[C:14]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)[O:15][C:16]=2[CH3:17])(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:60]([NH2:67])[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C=O)C.CCOC(C)=O>[CH2:60]([NH:67][C:22](=[O:24])[C:21]1[CH:20]=[CH:19][C:18]([C:14]2[O:15][C:16]([CH3:17])=[C:12]([CH2:11][S:8]([C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=3)(=[O:10])=[O:9])[N:13]=2)=[CH:26][CH:25]=1)[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68278368HCID 68278368, compound

Product 1

HCID 68278257HCID 68278257, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

Benzoic acid 29 (150 mg, 0.34 mmol) was dissolved in anhydrous DMF (5 mL), DIEA (0.12 mL, 0.69 mmol) and HBTU (171 mg, 0.45 mmol) were successively added and the reaction mixture was stirred at 20° C. for 10 min. Benzylamine (0.16 mL, 1.4 mmol) was added and the reaction mixture was stirred at 20° C. for 1 h. The mixture was diluted with EtOAc (150 mL), washed with H2O (3×50 mL), washed with brine (50 mL) and dried. The solvent evaporated and the residue was purified by column chromatography, eluting with a gradient (50-100%) of EtOAc/pet. ether followed by a gradient (1-4%) MeOH/DCM, to afford amide 57 (117 mg, 66%) as a white solid: mp (DCM/MeOH) 234-237° C.; 1H NMR δ □ (t, J=5.9 Hz, 1H, CONH), 8.01 (br d, J=8.6 Hz, 2H, H-2, H-6), 7.87 (br d, J=8.7 Hz, 2H, H-3, H-5), 7.85 (dt, J=8.8, 2.1 Hz, 2H, H-2′, H-6′), 7.72 (dt, J=8.7, 2.1 Hz, 2H, H-3′, H-5′), 7.34 (s, 2H, H-2″, H-6″), 7.33 (s, 2H, H-3″, H-5″), 7.22-7.28 (m, 1H, H-4″), 4.74 (s, 2H, CH2SO2), 4.49 (d, J=5.9 Hz, 2H, CH2NH), 2.21 (s, 3H, CH3); 13C NMR δ□ 165.3, 158.0, 150.0, 139.4, 137.7, 135.6, 132.2 (2), 130.3 (2), 128.6, 128.2 (2), 128.1, 128.0 (2), 127.2 (2), 126.7, 125.6, 125.3 (2), 52.6, 42.6, 9.7; MS m/z 526.5, 528.5 (MH+, 100%). Anal. calcd for C25H21BrN2O4S: C, 57.15; H, 4.03; N, 5.33. Found: C, 57.34; H, 3.74; N, 5.50%.

Workup

  1. stirringthe reaction mixture was stirred at 20° C. for 1 h
  2. washwashed with H2O (3×50 mL)
  3. washwashed with brine (50 mL)
  4. customdried
  5. customThe solvent evaporated
  6. customthe residue was purified by column chromatography
  7. washeluting with a gradient (50-100%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-bf1efed1145a42e99dc10999c7676d2f
Source dataset
uspto-grants-2016_03
Patent number
US09296732B2

Reaction notes

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