Ammonia → HCID 118037436, compound

HRID 1508792Notes

Reaction equation

[CH:1]1([O:6][C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][C:10]3=[C:9]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26]C)=O)=[CH:19][CH:18]=3)[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl-:28].[NH4+:29].N>CO>[ClH:28].[CH:1]1([O:6][C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][C:10]3=[C:9]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([NH2:29])=[O:26])=[CH:19][CH:18]=3)[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

A 20-mL vial was charged with methyl 2-(4-((2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetate (0.038 g, 0.10 mmol) and ammonium chloride (0.017 g, 0.31 mmol). To this was added methanol (3 mL) followed by NH3 (4.0 mL, 7N in methanol, 28 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 42 hr. The crude reaction solution concentrated under reduced pressure. The residue was adsorbed onto silica then purified by chromatography on silica using dichloromethane/methanol (10:0 to 1:1) as eluent, followed by preparative HPLC (water/acetonitrile with 0.05% TFA), to afford the title compound (0.019 g, 54%) as a yellow solid. MW=386.91. M.p. 78-80° C. 1H NMR (DMSO-d6, 500 MHz) δ 7.43 (br s, 1H), 7.18 (d, J=8.0 Hz, 2H), 7.14 (d, J=8.0 Hz, 2H), 6.83 (br s, 1H), 6.51 (br s, 1H), 5.31-5.25 (m, 1H), 3.86 (s, 2H), 3.32 (s, 2H), 2.84 (t, J=7.5 Hz, 2H), 2.73 (t, J=7.5 Hz, 2H), 2.02 (quin, J=7.5 Hz, 2H), 1.96-1.86 (m, 2H), 1.73-1.63 (m, 4H), 1.62-1.53 (m, 2H); APCI MS m/z 351 [M+H]+.

Workup

customThe vial was sealed
customThe crude reaction solution
concentrationconcentrated under reduced pressure
customthen purified by chromatography on silica

Sources & evidence

ORD record: ord-a5d890b3ff9f4848983ad953db08e544
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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