Trifluoroacetic acid → HCID 66604633, compound

HRID 2410813Notes

Reaction equation

HRID 2410813 reaction equation
[N:1](C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:41]=[C:42]([C:60]([NH2:62])=[O:61])[C:43]3[NH:44][C:45]4[CH:46]=[C:47]([N:53]5[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55][CH2:54]5)[CH:48]=[CH:49][C:50]=4[C:51]=3[N:52]=2)[CH:36]=[CH:37][C:38]=1[OH:39].[O:63]1[CH2:68][CH2:67][N:66]([CH2:69][CH2:70]O)[CH2:65][CH2:64]1.C(O)(C(F)(F)F)=O>C1COCC1.CO.O>[NH3:1].[Cl:32][C:33]1[CH:34]=[C:35]([C:40]2[CH:41]=[C:42]([C:60]([NH2:62])=[O:61])[C:43]3[NH:44][C:45]4[CH:46]=[C:47]([N:53]5[CH2:54][CH2:55][N:56]([CH3:59])[CH2:57][CH2:58]5)[CH:48]=[CH:49][C:50]=4[C:51]=3[N:52]=2)[CH:36]=[CH:37][C:38]=1[O:39][CH2:70][CH2:69][N:66]1[CH2:67][CH2:68][O:63][CH2:64][CH2:65]1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 136340637HCID 136340637, compound

Product 2

HCID 222AmmoniaHCID 66604633HCID 66604633, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (0.076 mL, 0.48 mmol) was added to a solution of triphenylphosphine (126 mg, 0.482 mmol), 2-(3-chloro-4-hydroxyphenyl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (70 mg, 0.16 mmol) and 2-morpholinoethanol (0.039 mL, 0.32 mmol) in dry THF (2 mL) in an oven-dried vial at RT under nitrogen. After stirring for 12 h, 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). SCX capture and release with 2 N NH3 in MeOH afforded 2-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (25 mg, 0.041 mmol, 26% yield) as a yellow solid. 1H NMR and LCMS are consistent with the desired material. MS (ESI) m/z 549.23 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.83 (1H, s), 8.27 (1H, d, J=8.55 Hz), 8.16 (1H, d, J=1.53 Hz), 8.00 (1H, dd, J=8.24, 1.83 Hz), 7.60 (1H, s), 7.08 (1H, d, J=8.24 Hz), 7.02 (1H, dd, J=8.70, 1.98 Hz), 6.93-6.96 (1H, m), 4.26-4.30 (2H, m), 3.76-3.81 (4H, m), 3.40-3.45 (4H, m), 2.90-2.95 (2H, m), 2.65-2.73 (8H, m), 2.44 (3H, s).

Sources & evidence

ORD record
ord-c7a1918f052947c688802f43eb674c9c
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…