4-Methylmorpholine → 4-(2-Fluorophenyl)-7-methyl-6-(pyrimidin-5-yloxy)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361255Notes

Reaction equation

HRID 2361255 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:20]2[C:19]3[C:14](=[CH:15][C:16]([CH3:28])=[C:17]([O:21][C:22]4[CH:23]=[N:24][CH:25]=[N:26][CH:27]=4)[CH:18]=3)[NH:13][C:12]=2[C:11]([C:29]([OH:31])=O)=[N:10][CH:9]=1.[Cl-].[NH4+].F[P-](F)(F)(F)(F)F.[N:41]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.CN1CCOCC1>CN(C=O)C.CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:20]2[C:19]3[C:14](=[CH:15][C:16]([CH3:28])=[C:17]([O:21][C:22]4[CH:23]=[N:24][CH:25]=[N:26][CH:27]=4)[CH:18]=3)[NH:13][C:12]=2[C:11]([C:29]([NH2:41])=[O:31])=[N:10][CH:9]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 679951684-(2-Fluorophenyl)-7-methyl-6-(pyrimidin-5-yloxy)-9H-pyrido[3,4-b]indole-1-carboxylic acid

Product 1

HCID 547664154-(2-Fluorophenyl)-7-methyl-6-(pyrimidin-5-yloxy)-9H-pyrido[3,4-b]indole-1-carboxamideYield 30.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A sealed vial containing 4-(2-fluorophenyl)-7-methyl-6-(pyrimidin-5-yloxy)-9H-pyrido[3,4-b]indole-1-carboxylic acid (0.0456 g, 0.110 mmol), ammonium chloride (0.024 g, 0.440 mmol), benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (0.063 g, 0.143 mmol), DIPEA (0.092 mL, 0.528 mmol) and N-methylmorpholine (0.047 mL, 0.429 mmol) in DMF (0.8 mL) was stirred. After 1 hr, the reaction was diluted with MeOH (1 mL) and subjected to autoprep reverse phase HPLC purification. The appropriate fractions were combined, basified with NaHCO3 (solid), and concentrated in vacuo. It was extracted with CH2Cl2 (3×). The organic layers were combined, dried over Na2SO4, and concentrated in vacuo to give the desired product (0.0137 g, 0.033 mmol, 30.1% yield) as a light tan solid, LC/MS (M+H)=414.10; 1H NMR (500 MHz, DMSO-d6) δ ppm 11.87 (br. S, 1 H), 8.98 (s, 1H), 8.47 (s, 2H), 8.33 (br. S, 1H), 8.26 (s, 1H), 7.81 (s, 2H), 7.59 (dd, J1=7.49, J2=1.39 Hz, 1H), 7.48-7.54 (m, 1H), 7.22-7.33 (m, 2H), 6.72 (s, 1H), 2.35 (s, 3 H).

Workup

  1. customsubjected to autoprep reverse phase HPLC purification
  2. concentrationconcentrated in vacuo
  3. extractionIt was extracted with CH2Cl2 (3×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-529c6f8a9cde4ca081e44fd31eb37b54
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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