Diisopropylethylamine → (+/-)-2-[[5-(2-Ethyl-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-N-[5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl]-4-oxazolecarboxamide

HRID 324410Notes

Reaction equation

HRID 324410 reaction equation
[CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=[S:34])[NH:20][C:21](=[O:33])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([OH:32])=O)[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2].[NH2:35][C:36]1[N:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[NH:38][N:37]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:1]([C:3]1[O:4][C:5]2[CH:12]=[CH:11][C:10]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:9]=3[CH:8]([C:18]3[C:19](=[S:34])[NH:20][C:21](=[O:33])[N:22]([CH2:24][C:25]4[O:26][CH:27]=[C:28]([C:30]([NH:35][C:36]5[N:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[NH:38][N:37]=5)=[O:32])[N:29]=4)[CH:23]=3)[C:6]=2[N:7]=1)[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 3508265-(trifluoromethyl)-4H-1,2,4-triazol-3-amineHCID 2733179PyBroPHCID 9826263(+/-)-2-[[5-(2-Ethyl-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-4-oxazolecarboxylic acid

Product 1

HCID 86756617(+/-)-2-[[5-(2-Ethyl-7-methyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-N-[5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl]-4-oxazolecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of the product of example 2 step (iii) (0.34 g), 4-(dimethylamino)pyridine (0.34 g), 3-amino-5-trifluoromethyl-1,2,4-triazole (J. Gen. Chem. USSR (Engl. Transl.) 1983, vol53, part 7, p1514) (0.42 g) and N,N-diisopropylethylamine (1.46 ml) in N,N-dimethylformamide (6 ml) was treated with bromo-tris(pyrrolidino)phosphonium hexafluorophosphate (1.3 g). After 2 hours the solution was quenched with aqueous tartaric acid. The solution was extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 30% ethyl acetate in toluene. The product was triturated with ethyl acetate/isohexane and the solid collected.

Workup

  1. customAfter 2 hours the solution was quenched with aqueous tartaric acid
  2. extractionThe solution was extracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated under reduced pressure
  6. customPurification
  7. washeluting with 30% ethyl acetate in toluene
  8. customThe product was triturated with ethyl acetate/isohexane
  9. customthe solid collected

Sources & evidence

ORD record
ord-ecd159ec57724d82b65ec4e0c69cef87
Source dataset
uspto-grants-2001_04
Patent number
US06218376B1

Reaction notes

Loading…