4-Methylmorpholine → 3-(2-Hydroxypropan-2-yl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(thiophen-3-yl)-1H-indazole-6-carboxamide

HRID 1047640Notes

Reaction equation

HRID 1047640 reaction equation
[OH:1][C:2]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14](O)=[O:15])=[CH:11][CH:12]=2)[N:7]([C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[N:6]=1)([CH3:4])[CH3:3].Cl.Cl.[CH3:24][C:25]1[N:29]=[C:28]([C@H:30]([NH2:32])[CH3:31])[O:27][N:26]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[OH:1][C:2]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([NH:32][C@@H:30]([C:28]3[O:27][N:26]=[C:25]([CH3:24])[N:29]=3)[CH3:31])=[O:15])=[CH:11][CH:12]=2)[N:7]([C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[N:6]=1)([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 666614513-(2-Hydroxypropan-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylic acidHCID 66661491(R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethanamine dihydrochloride

Product 1

HCID 469461723-(2-Hydroxypropan-2-yl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(thiophen-3-yl)-1H-indazole-6-carboxamideYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(2-Hydroxypropan-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylic acid (457.8 mg, 1.514 mmol), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (374.3 mg, 1.871 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (600.2 mg, 3.13 mmol), 1-hydroxy-7-azabenzotriazole (105.3 mg, 0.774 mmol), and N-methylmorpholine (670 μl, 6.09 mmol) were dissolved in N,N-dimethylformamide (15 mL) 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 1 mL) and trifluoroacetic acid (ca 1 mL). The reaction mixture was purified directly by preparative HPLC (reverse phase (C-18)), eluting with acetonitrile/water 0.1% trifluoracetic acid, to give the title compound (559.5 mg, 1.360 mmol, 90% yield) as a white solid. FIRMS: [M+1]=412.1452. 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H); 8.06 (d, J=8.5 Hz, 1H); 7.54 (dd, J=8.5, 1.4 Hz, 1H); 7.52-7.46 (m, 2H); 6.89 (d, J=7.7 Hz, 1H); 5.65-5.56 (m, 1H); 2.83 (s, 1H); 2.40 (s, 3H); 1.81 (s, 6H); 1.73 (d, J=7.1 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-6c6544fd7fdc4c44a1de2a788790bda9
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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