Acetic Acid → HCID 24826087, compound

HRID 1673151Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[NH:14][C:13]3[CH:15]=[CH:16][CH:17]=[C:18]([C:19]([NH2:21])=[O:20])[C:12]=3[N:11]=2)=[CH:6][CH:5]=1)(=O)[CH3:2].[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[N:22]1([CH:1]([C:4]2[CH:9]=[CH:8][C:7]([C:10]3[NH:14][C:13]4[CH:15]=[CH:16][CH:17]=[C:18]([C:19]([NH2:21])=[O:20])[C:12]=4[N:11]=3)=[CH:6][CH:5]=2)[CH3:2])[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of EXAMPLE 34A (0.1 g, 0.4 mmol) and pyrrolidine (0.13 mL, 1.6 mmol) in methanol (1 mL) was treated with sodium cyanoborohydride (0.05 g, 0.8 mmol) and acetic acid (0.2 mL) and the mixture stirred overnight at 70° C. The residue was concentrated and purified by flash chromatography on silica gel using 0-10% dichloromethane/methanol/0.1% ammonium hydroxide to provide the title compound, which was dissolved in methanol (1 mL), treated with a solution of 1M hydrochloric acid in ether (2 mL) and stirred at ambient temperature for 2 hours. The precipitate was filtered to give the title compound as the hydrochloride salt. 1H NMR (DMSO-d6) δ 11.26 (s, 1H), 8.34 (d, J=8.4 Hz, 2H), 7.85-7.91 (m, 3H), 7.79 (d, J=7.2 Hz, 2H), 7.39 (t, J=7.8 Hz, 1H), 4.51 (qd, J=7.4, 7.2 Hz, 1H), 3.70 (dd, J=11.4, 4.5 Hz, 1H), 3.12-3.20 (m, 1 Hz), 2.95-3.02 (m, 1H), 2.89 (dq, J=11.2, 8.1 Hz, 1H), 1.91-2.00 (m, 2H), 1.79-1.88 (m, 1H), 1.69 (d, J=6.9 Hz, 3H).

Workup

concentrationThe residue was concentrated
custompurified by flash chromatography on silica gel using 0-10% dichloromethane/methanol/0.1% ammonium hydroxide

Sources & evidence

ORD record: ord-08b3a5df88e047fb81baa6252d722750
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999117B2

Reaction notes

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