Aniline → 7-Difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid[3-(morpholine-4-sulfonyl)-phenyl]-amide

HRID 2224411Notes

Reaction equation

HRID 2224411 reaction equation
[F:1][CH:2]([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]([OH:14])=O)=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[N:26]1([S:32]([C:35]2[CH:36]=[C:37]([NH2:41])[CH:38]=[CH:39][CH:40]=2)(=[O:34])=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.N1N2C=CC=NC2=C(C(O)=O)C=1.C(Cl)(=O)C(Cl)=O.NC1C=CC=CC=1>C1COCC1.CN(C=O)C.CN(C)C1C=CN=CC=1>[N:26]1([S:32]([C:35]2[CH:36]=[C:37]([NH:41][C:12]([C:11]3[CH:10]=[N:9][N:8]4[C:3]([CH:2]([F:25])[F:1])=[CH:4][C:5]([C:15]5[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:17][CH:16]=5)=[N:6][C:7]=34)=[O:14])[CH:38]=[CH:39][CH:40]=2)(=[O:34])=[O:33])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1

Participants

9

Reactant 5

HCID 6115AnilineHCID 65578Oxalyl chlorideHCID 5594103-(Morpholine-4-sulfonyl)anilineHCID 1910189Pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 666502687-Difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 692928077-Difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid[3-(morpholine-4-sulfonyl)-phenyl]-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The title compound was prepared from 7-difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.1) and 3-(morpholine-4-sulfonyl)-phenylamine [CAS 22184-97-0; commercially available] according to general procedure II as follows: to a stirred solution of a pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (1.0 mmol) in THF (4 ml) was added at room temperature DMF (2 drops), the solution was cooled to 0° C. and oxalylchloride (1.5 mmol) was added. The reaction mixture was stirred at room temperature for 3 h and evaporated to dryness. The precipitate was dissolved in pyridine (6 ml) and, while stirring at room temperature, 4-dimethylaminopyridine (1 mmol) and an aniline derivative (1 mmol) was added. The reaction mixture was allowed to stir at room temperature for 16 h, evaporated to dryness and the crude product purified by flash chromatography on silica gel (20 g, dichloromethane/methanol) to yield the product as a light yellow solid, which was further purified by crystallization from methanol/hexane. MS (ISP) 580.1 [(M−H)−]; mp 221° C.

Workup

  1. customevaporated to dryness
  2. dissolutionThe precipitate was dissolved in pyridine (6 ml)
  3. stirringwhile stirring at room temperature
  4. stirringto stir at room temperature for 16 h
  5. customevaporated to dryness
  6. customthe crude product purified by flash chromatography on silica gel (20 g, dichloromethane/methanol)

Sources & evidence

ORD record
ord-f0e397402b044c35830bffa8a18942b0
Source dataset
uspto-grants-2008_05
Patent number
US07378417B2

Reaction notes

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