4-Methylmorpholine → 4-(3-(4-(Dimethylamino)benzamido)-2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361357Notes

Reaction equation

HRID 2361357 reaction equation
[CH3:1][N:2]([CH3:41])[C:3]1[CH:40]=[CH:39][C:6]([C:7]([NH:9][C:10]2[C:11]([F:38])=[C:12]([C:16]3[C:28]4[C:27]5[C:22](=[CH:23][C:24]([N:29]6[CH2:34][CH2:33][O:32][CH2:31][CH2:30]6)=[CH:25][CH:26]=5)[NH:21][C:20]=4[C:19]([C:35]([OH:37])=O)=[N:18][CH:17]=3)[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][CH:4]=1.[Cl-].[NH4+].C([N:47](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CO>[CH3:41][N:2]([CH3:1])[C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[C:11]([F:38])=[C:12]([C:16]3[C:28]4[C:27]5[C:22](=[CH:23][C:24]([N:29]6[CH2:34][CH2:33][O:32][CH2:31][CH2:30]6)=[CH:25][CH:26]=5)[NH:21][C:20]=4[C:19]([C:35]([NH2:47])=[O:37])=[N:18][CH:17]=3)[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:39][CH:40]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 679950664-(3-(4-(Dimethylamino)benzamido)-2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylic acid

Product 1

HCID 706516814-(3-(4-(Dimethylamino)benzamido)-2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamideYield 23.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(3-(4-(dimethylamino)benzamido)-2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylic acid (105 mg, 0.190 mmol), ammonium chloride (40.6 mg, 0.759 mmol), N,N-diisopropylethylamine (0.159 mL, 0.910 mmol), BOP (109 mg, 0.247 mmol), N-methylmorpholine (0.081 mL, 0.740 mmol) in DMF (0.5 mL) was stirred at room temperature for 1.5 hr. The mixture was diluted with MeOH (4 mL), divided into three portions, and purified by reverse phase HPLC. The correct fractions were concentrated under vacuum and basified with saturated NaHCO3 solution to pH 10. The precipitating product (24.7 mg, 0.044 mmol, 23.09% yield) was collected as a yellow solid by suction filtration and dried at 50° C. under vacuum. LCMS (M+H)+=553.32. 1H NMR (500 z, DMSO-d6) δ: 11.52 (s, 1H), 9.86 (s, 1H), 8.31 (s, 1H), 8.20 (s, 1H), 7.90 (d, J=9.0 Hz, 2H), 7.84 (m, 1H), 7.76 (s, 1H), 7.45-7.40 (m, 2H), 7.32 (d, J=8.0 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 6.86 (dd, J1=9.0 Hz, J2=2.0 Hz, 1H), 6.77 (d, J=9.0 Hz, 2H), 3.79-3.77 (m, 4H), 3.22-3.19 (m, 4H), 2.51 (m, 6H).

Workup

  1. custompurified by reverse phase HPLC
  2. concentrationThe correct fractions were concentrated under vacuum

Sources & evidence

ORD record
ord-bcde4d8ea73949598c33139e133bd1c1
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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