Potassium Carbonate → 1-(2-Amino-4,5,7,8-tetrahydro-thiazolo (4,5-d) azepin-6-yl)-2-[3,5-bis-(4-fluoro-phenyl)-pyrazol-1-yl]-ethanone

HRID 400488Notes

Reaction equation

HRID 400488 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:10]([CH2:20][C:21](O)=[O:22])[N:9]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Br.[S:34]1[C:43]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38][C:37]=2[N:36]=[C:35]1[NH2:44].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[NH2:44][C:35]1[S:34][C:43]2[CH2:42][CH2:41][N:40]([C:21](=[O:22])[CH2:20][N:10]3[C:11]([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=4)=[CH:12][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:9]3)[CH2:39][CH2:38][C:37]=2[N:36]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 866860295,6,7,8-tetrahydro-4H-Thiazolo[4,5-d]azepin-2-amine hydrobromideHCID 86686085(3,5-Bis-(4-fluoro-phenyl)-pyrazol-1-yl)-acetic acid

Product 1

HCID 715865471-(2-Amino-4,5,7,8-tetrahydro-thiazolo (4,5-d) azepin-6-yl)-2-[3,5-bis-(4-fluoro-phenyl)-pyrazol-1-yl]-ethanoneYield 52.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

100 mg (3,5-bis-(4-fluoro-phenyl)-pyrazol-1-yl)-acetic acid was dissolved in 2 mL DMF. 165 mg PFTU and 170 μL DIPEA were added to this solution and the mixture was stirred for 15 min at RT. Then, 160 mg 5,6,7,8-Tetrahydro-4H-thiazolo (4,5-d) azepin-2-ylamine hydrobromide was added and the reaction was stirred over night. Then, K2CO3 solution (5%) and CH2Cl2 were added, the organic phase was separated and washed two times with water. The solvent was removed and the residue was purified by HPLC (method 1) to give 78 mg of the desired compound. Rt: 0.80 min (method C), (M+H)+: 466

Workup

  1. stirringthe reaction was stirred over night
  2. customthe organic phase was separated
  3. washwashed two times with water
  4. customThe solvent was removed
  5. customthe residue was purified by HPLC (method 1)

Sources & evidence

ORD record
ord-134a8977589c4316960f7636866a73ff
Source dataset
uspto-grants-2014_06
Patent number
US08741892B2

Reaction notes

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