Acetic Anhydride → HCID 53251278, compound

HRID 2407192Notes

Reaction equation

HRID 2407192 reaction equation
C(O[C:5](=[O:7])[CH3:6])(=O)C.[CH3:8][C:9]1[N:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]2[C:25]3[NH:24][C:23]4[CH2:26][CH2:27][NH:28][CH2:29][C:22]=4[C:21]=3[CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1>C(O)(=O)C>[C:5]([N:28]1[CH2:27][CH2:26][C:23]2[NH:24][C:25]3[C:17](/[CH:16]=[CH:15]/[C:12]4[CH:13]=[N:14][C:9]([CH3:8])=[CH:10][CH:11]=4)=[CH:18][CH:19]=[CH:20][C:21]=3[C:22]=2[CH2:29]1)(=[O:7])[CH3:6]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 53251119HCID 53251119, compound

Product 1

HCID 53251278HCID 53251278, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Acetic anhydride (1 mL; Fischer) was added dropwise to a solution of the product of Example 6C (45 mg, 0.16 mmol) in acetic acid (1 mL). The reaction mixture was stirred at room temperature for 10 minutes and then concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4) (1:1 mixture of amide rotamers observed) δ ppm 2.23 and 2.24 (two s, 3H; amide rotamers), 2.54 (s, 3H), 2.90 and 2.99 (two t, J=5.8 Hz, 2H; amide rotamers), 3.91 and 3.99 (two t, J=5.8 Hz, 2H; amide rotamers), 4.74-4.77 (m, 2H), 7.05 and 7.06 (two t, J=7.6 Hz, 2H; amide rotamers), 7.24 (d, J=16.5 Hz, 1H), 7.31 (d, J=8.2 Hz, 1H), 7.36 and 7.39 (two dd, J=7.8, 0.8 Hz, 1H; amide rotamers), 7.42 and 7.43 (two d, J=7.3 Hz, 1H), 7.67 (d, J=16.5 Hz, 1H), 8.00 and 8.02 (two t, J=1.8 Hz, 1H), 8.61 (d, J=2.1 Hz, 1H); MS (APCI) m/z 332 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-9959e9944e2e4d02b531a37ed1998aa3
Source dataset
uspto-grants-2014_08
Patent number
US08809532B2

Reaction notes

Loading…