4-Methylmorpholine → HCID 46945972, compound

HRID 1047621Notes

Reaction equation

HRID 1047621 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]2[CH:22]=[C:21]([C:23](O)=[O:24])[S:20][C:11]=2[N:12]([C:14]2[CH:19]=[N:18][CH:17]=[CH:16][N:15]=2)[N:13]=1.Cl.C[N:28](C)CCCN=C=NCC.[OH:38][N:39]1[C:43]2[N:44]=[CH:45][CH:46]=[CH:47][C:42]=2N=N1.CN1CCOCC1>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]2[CH:22]=[C:21]([C:23]([NH:28][C@@H:46]([C:45]3[O:38][N:39]=[C:43]([CH3:42])[N:44]=3)[CH3:47])=[O:24])[S:20][C:11]=2[N:12]([C:14]2[CH:19]=[N:18][CH:17]=[CH:16][N:15]=2)[N:13]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66661384HCID 66661384, compound

Product 1

HCID 46945972HCID 46945972, compoundYield 121.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-(2,4-Difluorophenyl)-1-(pyrazin-2-yl)-1H-thieno[2,3-c]pyrazole-5-carboxylic acid (43.6 mg, 0.069 mmol, with 4 equivalents of sodium chloride), L-(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (17.2 mg, 0.086 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (28.5 mg, 0.149 mmol), 1-hydroxy-7-azabenzotriazole (5.2 mg, 0.038 mmol), and N-methylmorpholine (31 μl, 0.282 mmol) were dissolved in N,N-dimethylformamide (700 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 (ca 0.2 mL). The reaction mixture was purified directly by preparative HPLC (Reverse phase (C-18)), eluting with acetonitrile/water 0.05% ammonium hydroxide, to give the title compound (21.5 mg, 0.046 mmol, 66.3% yield) as a white solid. HRMS [M+1] found=468.1063. 1H. NMR (500 MHz, CDCl3): δ 9.45 (s, 1H); 8.54-8.46 (m, 2H); 8.20-8.13 (m, 1H); 7.74 (d, J=3.9 Hz, 1H); 7.10-7.04 (m, 1H); 7.03-6.97 (m, 1H); 6.89 (d, J=7.8 Hz, 1H); 5.63 (t, J=7.3 Hz, 1H); 2.44 (s, 3H); 1.74 (d, J=7.1 Hz, 3H).

Workup

  1. customquenched by addition of water (ca 0.2 mL) and trifluoroacetic acid (ca 0.2 mL)
  2. customThe reaction mixture was purified directly by preparative HPLC (Reverse phase (C-18))
  3. washeluting with acetonitrile/water 0.05% ammonium hydroxide

Sources & evidence

ORD record
ord-ba4949e24a7443a4834d745ace8f89f2
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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