4-Methylmorpholine → 2-(Chlorophenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-1H-indazole-5-carboxamide

HRID 1047645Notes

Reaction equation

HRID 1047645 reaction equation
ClC1C=CC=CC=1[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17](O)=[O:18])[CH:15]=2)[N:10]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:9]=1.[ClH:27].Cl.[CH3:29][C:30]1[N:34]=[C:33]([C@H:35]([NH2:37])[CH3:36])[O:32][N:31]=1.Cl.CN(C)[CH2:41][CH2:42][CH2:43]N=C=NCC.ON1[C:55]2N=CC=[CH:59][C:54]=2N=N1.CN1CCOCC1>CN(C)C=O>[Cl:27][C:41]1[CH:42]=[CH:43][CH:59]=[CH:54][C:55]=1[N:9]1[CH2:8][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]([NH:37][C@@H:35]([C:33]3[O:32][N:31]=[C:30]([CH3:29])[N:34]=3)[CH3:36])=[O:18])[CH:15]=2)[N:10]1[C:20]1[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 666614063-(2-Chlorophenyl)-1-(4-methylphenyl)-1H-indazole-5-carboxylic acidHCID 66661491(R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethanamine dihydrochloride

Product 1

HCID 866612742-(Chlorophenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-1H-indazole-5-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(2-Chlorophenyl)-1-(4-methylphenyl)-1H-indazole-5-carboxylic acid (30.6 mg, 0.046 mmol, with 4 equivalents of sodium chloride), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (13.72 mg, 0.069 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (17.52 mg, 0.091 mmol), 1-hydroxy-7-azabenzotriazole (3.11 mg, 0.023 mmol), and N-methylmorpholine (20.10 μl, 0.1.83 mmol) were dissolved in N,N-dimethylformamide (457 μl) at 25° C. The reaction mixture was heated to 50° C. and allowed to stir for 10 min. The reaction was stopped, quenched by addition of water (ca 0.2 mL) and trifluoroacetic acid (ea 0.2 mL). The reaction mixture was purified directly by preparative HPLC (Reverse phase (C-18)), eluting with acetonitrile/water 0.1% trifluoroacetic acid, to give the title compound (16.2 mg, 0.023 mmol, 50.6% yield) as a white solid. HRMS [M+1]=472.1532. 1H NMR (400 MHz, CDCl3): δ 8.17 (s, 1H); 7.88 (dd, J=8.9, 1.7 Hz, 1H); 7.74 (d, J=8.9 Hz, 1H); 7.65-7.60 (m, 3H); 7.56-7.53 (m, 1H); 7.42-7.38 (m, 2H); 7.34 (d, J=8.1 Hz, 2H); 6.79 (d, J=7.7 Hz, 1H); 5.58 (t, J=7.3 Hz, 1H); 2.42 (s, 3H); 2.36 (s, 3H); 1.68 (d, J=7.1 Hz, 3H).

Workup

  1. customquenched by addition of water (ca 0.2 mL) and trifluoroacetic acid (ea 0.2 mL)
  2. customThe reaction mixture was purified directly by preparative HPLC (Reverse phase (C-18))
  3. washeluting with acetonitrile/water 0.1% trifluoroacetic acid

Sources & evidence

ORD record
ord-5aa397d781c74f6c94072353fad3e917
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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