Diisopropylethylamine → tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

HRID 1915868Notes

Reaction equation

HRID 1915868 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22](O)=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:58][C:59]1[CH:60]=[N:61][N:62]([CH3:79])[C:63]=1[N:64]1[CH2:70][CH2:69][CH:68]([F:71])[CH:67]([NH:72][C:73](=[O:78])[C:74]([F:77])([F:76])[F:75])[CH2:66][CH2:65]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([F:20])[C:14]=1[C:12]1[S:13][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[C:10]([C:22](=[O:23])[NH:58][C:59]2[CH:60]=[N:61][N:62]([CH3:79])[C:63]=2[N:64]2[CH2:65][CH2:66][CH:67]([NH:72][C:73](=[O:78])[C:74]([F:75])([F:76])[F:77])[CH:68]([F:71])[CH2:69][CH2:70]2)[N:11]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86680076N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide

Product 1

HCID 86680075tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamateYield 99.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (784 mg, 2.2 mmol) in DCM (40 mL) was added PyBOP (1.46 g, 2.8 mmol) and the mixture stirred at room temperature for 30 min. A solution of N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide (647 mg, 2.0 mmol) and DIPEA (0.59 mL, 3.4 mmol) in DCM (40 mL) was then added and the mixture was stirred at room temperature for 16 hr. The mixture was diluted with DCM (60 mL) and washed with water (30 mL). The organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as an off-white solid (1.32 g).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hr
  2. washwashed with water (30 mL)
  3. customThe organic layer was separated
  4. custompassed through a phase separation cartridge
  5. customthe solvent removed under reduced pressure
  6. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-ce1346a39b0d4cf48ac596b7dda64bb7
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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