Ammonia → N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide

HRID 1098959Notes

Reaction equation

HRID 1098959 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]([O-:9])=O)=[N:4][N:3]=1.[K+].C(Cl)(=O)C(Cl)=O.[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:32]3[C:27](=[CH:28][C:29]([O:33][C@H:34]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=4)[C@@H:35]([NH2:37])[CH3:36])=[CH:30][CH:31]=3)[CH:26]=[N:25]2)=[CH:20][CH:19]=1.C(N(CC)C(C)C)(C)C.N>C1COCC1.CCOC(C)=O.C(#N)C>[F:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[C:32]3[C:27](=[CH:28][C:29]([O:33][C@H:34]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=4)[C@@H:35]([NH:37][C:7]([C:5]4[O:6][C:2]([CH3:1])=[N:3][N:4]=4)=[O:9])[CH3:36])=[CH:30][CH:31]=3)[CH:26]=[N:25]2)=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 24820502Potassium 5-methyl-1,3,4-oxadiazole-2-carboxylateHCID 59339733(1R,2S)-1-(1-(4-fluorophenyl)indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

Product 1

HCID 44515376N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

Potassium 5-methyl-[1,3,4]oxadiazole-2-carboxylate (31.8 mg, 0.19 mmol) was mixed with acetonitrile (195 μl). A slurry was formed. The mixture was cooled to 0-5° C. oxalyl chloride (14.99 μl, 0.17 mmol) was added and the reaction was stirred for 1 h at 0-5° C. (1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (6a, 25 mg, 0.06 mmol) was dissolved in dry THF (400 μl). N,N-diisopropylethylamine (65.6 μl, 0.38 mmol) was added. The THF solution was cooled to 0-5° C. The acid chloride slurry was drop wise added to the amine solution. The reaction was stirred at 0-5° C. After 1.5 h the reaction was poured into a mixture of EtOAc and diluted ammonia (ca 5%). The mixture was shaken, the organic layer collected. The water phase was washed twice with EtOAc. The combined organic layers were dried over sodium sulphate.

Workup

  1. customA slurry was formed
  2. additionwas added
  3. stirringThe mixture was shaken
  4. customthe organic layer collected
  5. washThe water phase was washed twice with EtOAc
  6. dry with materialThe combined organic layers were dried over sodium sulphate

Sources & evidence

ORD record
ord-8892e378c8674706a38778a51c6da2cb
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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