Ammonium Acetate → 1-[8-Chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-yl]ethanamine

HRID 717823Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[N:4]([CH:18]=[N:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([C:8](=O)[CH3:9])[CH:7]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:27].[Na+]>CO>[Cl:1][C:2]1[C:3]2[N:4]([CH:18]=[N:19][CH:20]=2)[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[C:6]([CH:8]([NH2:27])[CH3:9])[CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

1-[8-Chloro-5-(3-fluorophenyl)imidazo[1,5-a]pyridine-6-yl]ethanone (0.12 g, 0.42 mmol) and ammonium acetate (0.32 g, 4.2 mmol) were stirred in methanol (4.6 mL) and heated to 65° C. for 1 hour. Sodium cyanoborohydride (78 mg, 1.3 mmol) was added and the mixture was heated at 65° C. for 16 hours. The mixture was evaporated and the resultant residue was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (51 mg, 42%). LCMS calculated for C15H14ClFN3 (M+H)+: m/z=290.1. found: 290.0. 1H NMR (300 MHz, DMSO-d6): δ 7.63 (m, 2H), 7.41 (m, 3H), 7.35 (m, 2H), 3.60 (m, 1H), 1.18 (m, 3H).

Workup

temperaturethe mixture was heated at 65° C. for 16 hours
customThe mixture was evaporated
customthe resultant residue was purified on RP-HPLC (XBridge C18 column
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record: ord-ffd49a2ec477422b8cd909c822f54aff
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193721B2

Reaction notes

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