Diisopropylethylamine → HCID 87401043, compound

HRID 1185262Notes

Reaction equation

HRID 1185262 reaction equation
[F:1][C:2]1([F:25])[CH2:8][CH2:7][N:6]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH2:5][CH2:4][CH:3]1[NH:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:68]([O:72][C:73]([NH:75][C:76]1[S:80][C:79]([C:81]2[C:86]([F:87])=[CH:85][CH:84]=[CH:83][C:82]=2[F:88])=[N:78][C:77]=1[C:89](O)=[O:90])=[O:74])([CH3:71])([CH3:70])[CH3:69]>CO.C(Cl)Cl.[Pd]>[F:1][C:2]1([F:25])[CH:3]([NH:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH2:4][CH2:5][N:6]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[NH:15][C:89]([C:77]2[N:78]=[C:79]([C:81]3[C:82]([F:88])=[CH:83][CH:84]=[CH:85][C:86]=3[F:87])[S:80][C:76]=2[NH:75][C:73](=[O:74])[O:72][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:90])[CH2:7][CH2:8]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 87400101HCID 87400101, compound

Product 1

HCID 87401043HCID 87401043, compoundYield 69.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-(5,5-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoroacetamide (0.29 g, 0.78 mmol) in MeOH (20 mL) was passed through the H-Cube® (Full H2 Mode, 70° C., flow rate: 1 mL/min, 30 mm 10% Pd/C cartridge). The solvent was removed under reduced pressure to give the crude amine. To a solution of this amine (0.26 g, 0.78 mmol) in DCM (15 mL) was added DIPEA (0.68 mL, 3.9 mmol), PyBOP (0.61 g, 1.17 mmol) and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (0.30 g, 0.86 mmol) and the mixture was stirred at room temperature for 18 hr. The mixture was diluted with DCM and washed with water. The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-80% EtOAc/isohexane) gave tert-butyl 4-(5-(4,4-difluoro-5-(2,2,2-trifluoroacetamido)-azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-(2,6-difluorophenyl)thiazol-5-ylcarbamate as a white solid (0.37 g, 69%). 1H NMR (400 MHz, CDCl3) δ 10.28 (s, 1H), 8.71 (s, 1H), 7.82 (s, 1H), 7.42-7.33 (m, 1H), 7.11-7.01 (m, 2H), 6.72 (d, J=9.0 Hz, 1H), 4.73-4.57 (m, 1H), 3.77 (s, 3H), 3.51-3.37 (m, 2H), 3.36-3.25 (m, 2H), 2.49-2.36 (m, 2H), 2.25-2.03 (m, 2H), 1.55 (s, 9H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto give the crude amine
  3. washwashed with water
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. customthe solvent removed under reduced pressure
  7. customPurification via silica gel column chromatography (0-80% EtOAc/isohexane)

Sources & evidence

ORD record
ord-e825ce30df6e45a587c01110a4b9c46b
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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