Ammonia → HCID 66605104, compound

HRID 2410825Notes

Reaction equation

HRID 2410825 reaction equation
[CH:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:17]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH:15]=[C:14]([C:28]([NH2:30])=[O:29])[C:10]=3[NH:11][C:12]=2[CH:13]=1)([CH3:3])[CH3:2].C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O.N>C(Cl)Cl.C1COCC1.CO.O>[CH:1]([N:4]([CH3:33])[C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:17]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=4)[CH:15]=[C:14]([C:28]([NH2:30])=[O:29])[C:10]=3[NH:11][C:12]=2[CH:13]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 222AmmoniaHCID 712FormaldehydeHCID 6422Trifluoroacetic acid2×HCID 5049666Sodium triacetoxyborohydrideHCID 66605060HCID 66605060, compound

Product 1

HCID 66605104HCID 66605104, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent4×HCID 962WaterSolvent2×HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A suspension of 7-(isopropylamino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (13 mg, 0.032 mmol), formaldehyde (0.023 mL, 0.315 mmol, 37% aq. solution), and sodium triacetoxyborohydride (33 mg, 0.16 mmol) in a mixture of DCM/THF (2/1) (0.3 mL) was stirred at RT overnight. The crude reaction was diluted with MeOH and preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, 10-60% B at 42 mL/min over 20 min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 7-(isopropyl(methyl)amino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (6 mg, 0.011 mmol, 38% yield). MS (ESI) m/z 427.13 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.17 (1H, br. s.), 8.60 (2H, d, J=1.53 Hz), 8.54 (1H, br. s.), 8.35 (1H, s), 8.03 (1H, d, J=8.85 Hz), 7.83 (1H, br. s), 7.73-7.78 (2H, m), 7.07 (1H, d, J=2.14 Hz), 6.87 (1H, dd, J=8.85, 2.14 Hz), 4.24 (septupled, 1H, J=6.6), 2.82 (3H, s), 1.21 (6H, d, J=6.41 Hz).

Workup

  1. customThe crude reaction

Sources & evidence

ORD record
ord-08cf8dc2959146e0a6fa06e68375577a
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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