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

HRID 239193Notes

Reaction equation

HRID 239193 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N: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.Br.[S:35]1[C:44]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39][C:38]=2[N:37]=[C:36]1[NH2:45].C(=O)([O-])O.[Na+]>CN(C=O)C.C(Cl)Cl>[NH2:45][C:36]1[S:35][C:44]2[CH2:43][CH2:42][N:41]([C:21](=[O:22])[CH2:20][N:10]3[C:11]([C:13]4[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=4)=[N:12][C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[N:9]3)[CH2:40][CH2:39][C:38]=2[N:37]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 199857845,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin-2-ylamine dihydrobromideHCID 86686517(3,5-bis-(4-Fluoro-phenyl)-(1,2,4)triazol-1-yl)-acetic acid

Product 1

HCID 866865231-(2-Amino-4,5,7,8-tetrahydro-thiazolo[4,5-d]azepin-6-yl)-2-(3,5-bis-(4-fluoro-phenyl)-(1,2,4)triazol-1-yl)-ethanoneYield 53.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

350 mg (3,5-bis-(4-fluoro-phenyl)-(1,2,4)triazol-1-yl)-acetic acid and 0.2 mL DIPEA were dissolved in 4.5 mL DMF. 570 mg PFTU was added to this solution and the mixture was stirred for 7 min at RT. Then, 333 mg 5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin-2-ylamine dihydrobromide and 0.4 mL DIPEA were added and the reaction was stirred over night at RT. Then, sodium hydrogencarbonate solution (10%) and CH2Cl2 were added, the organic phase was separated and the solvent was removed. The residue was purified by HPLC to yield 252 mg of the desired compound.

Workup

  1. addition570 mg PFTU was added to this solution
  2. stirringthe reaction was stirred over night at RT
  3. customthe organic phase was separated
  4. customthe solvent was removed
  5. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-84a199eadd7a445f89b07b5e7c50674a
Source dataset
uspto-grants-2014_02
Patent number
US08642774B2

Reaction notes

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