Ammonia → HCID 66604175, compound

HRID 2410765Notes

Reaction equation

[CH3:1][C@H:2]1[CH2:7][N:6]([C:8]2[CH:9]=[CH:10][C:11]3[C:12]4[N:20]=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=5)[CH:18]=[C:17]([C:31]([O:33]C)=O)[C:13]=4[NH:14][C:15]=3[CH:16]=2)[CH2:5][C@@H:4]([CH3:35])[O:3]1.[NH3:36]>CO>[CH3:35][C@H:4]1[CH2:5][N:6]([C:8]2[CH:9]=[CH:10][C:11]3[C:12]4[N:20]=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=5)[CH:18]=[C:17]([C:31]([NH2:36])=[O:33])[C:13]=4[NH:14][C:15]=3[CH:16]=2)[CH2:7][C@@H:2]([CH3:1])[O:3]1

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of methyl 7-((2S,6R)-2,6-dimethylmorpholino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (16 mg, 0.033 mmol) in 7 N NH3 in MeOH (5 mL) in a sealed microwave vial was heated at 80° C. for 48 hr. Removal of the solvent followed by preparative HPLC (100×30 mm Luna C18 column, gradient elution with A:B=75:25 to A:B=25:75 [A=95% H2O:5% MeOH:0.1% TFA; B=5% H2O:95% MeOH:0.1% TFA] over 20 min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 7-((2S,6R)-2,6-dimethylmorpholino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (12.9 mg, 0.026 mmol, 79% yield) as an orange solid. MS (ESI) m/z 469.28 (M+H). 1H NMR (500 MHz, MeOD) δ ppm 8.47 (1H, s), 8.39 (1H, t, J=4.27 Hz), 8.23 (1H, d, J=8.55 Hz), 8.20 (1H, s), 7.72(2H, d, J=4.27 Hz), 7.07-7.11 (1H, m), 7.01-7.08 (1H, m), 3.80-3.91 (2H, m), 3.70-3.76 (2H, m), 2.43-2.53 (2H, m), 1.29 (6H, d, J=6.41 Hz).

Workup

customRemoval of the solvent
wash100×30 mm Luna C18 column, gradient elution with A:B=75:25 to A:B=25:75 [A=95% H2O

Sources & evidence

ORD record: ord-29bc72ac229847ac9948ac0e21de8fb3
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815840B2

Reaction notes

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