[(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester → (R)-5-amino-N-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-(trifluoromethyl)phenyl)thiazole-4-carboxamide

HRID 2089351Notes

Reaction equation

HRID 2089351 reaction equation
C(OC(=O)[NH:10][C@@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[N:19]([CH3:49])[N:20]=[CH:21][C:22]=2[NH:23][C:24]([C:26]2[N:27]=[C:28]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[C:45]([F:48])([F:47])[F:46])[S:29][C:30]=2[NH:31]C(OC(C)(C)C)=O)=[O:25])[CH2:13][CH2:12]1)C1C=CC=CC=1>O1CCOCC1.Cl>[NH2:31][C:30]1[S:29][C:28]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[C:45]([F:47])([F:48])[F:46])=[N:27][C:26]=1[C:24]([NH:23][C:22]1[CH:21]=[N:20][N:19]([CH3:49])[C:18]=1[N:14]1[CH2:15][CH2:16][CH2:17][C@@H:11]([NH2:10])[CH2:12][CH2:13]1)=[O:25]

Participants

4

Reactant 1

HCID 58464975[(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester

Product 1

HCID 58464822(R)-5-amino-N-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-(trifluoromethyl)phenyl)thiazole-4-carboxamideYield 59.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A heterogeneous mixture of [(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester (83.9 mg, 0.117 mmol) in 1,4-dioxane (1.0 mL) and 2M aq. HCl (10 mL) was stirred at 120° C. under N2 for 16 h. The resultant homogeneous reaction was then slowly quenched with saturated aq. NaHCO3 solution and then extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified via reverse phase HPLC to afford 210 (33.4 mg, 59.2%) as a white solid. 1H NMR (400 MHz, DMSO) δ 8.51 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.78 (d, J=4.1 Hz, 2H), 7.68 (dd, J=8.1 Hz, 3.9 Hz, 1H), 7.58 (s, 1H), 7.46 (broad s, 2H), 3.64 (s, 3H), 3.10 (t, J=5.3 Hz, 4H), 3.02-2.90 (m, 1H), 1.89-1.73 (m, 3H), 1.64-1.44 (m, 3H); 2 protons buried in water peak; MS (ESI) m/z: 480.1 [M+H]+

Workup

  1. customThe resultant homogeneous reaction
  2. customwas then slowly quenched with saturated aq. NaHCO3 solution
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-f153785352c04f81a8ba5b136c27e712
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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