Hydrochloric Acid → 2-[(6-{[4-(Aminomethyl)-1H-1,2,3-triazol-1-yl]methyl}pyridin-2-yl)amino]-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

HRID 386046Notes

Reaction equation

HRID 386046 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[N:10]=[N:11][N:12]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22]3[S:23][C:24]([C:30]4[C:35]([F:36])=[CH:34][C:33]([C:37]([OH:40])([CH3:39])[CH3:38])=[CH:32][C:31]=4[F:41])=[CH:25][C:26]=3[C:27]([NH2:29])=[O:28])[N:16]=2)[CH:13]=1)(C)(C)C.Cl.O1CCOCC1>CCOC(C)=O>[NH2:7][CH2:8][C:9]1[N:10]=[N:11][N:12]([CH2:14][C:15]2[N:16]=[C:17]([NH:21][C:22]3[S:23][C:24]([C:30]4[C:31]([F:41])=[CH:32][C:33]([C:37]([OH:40])([CH3:38])[CH3:39])=[CH:34][C:35]=4[F:36])=[CH:25][C:26]=3[C:27]([NH2:29])=[O:28])[CH:18]=[CH:19][CH:20]=2)[CH:13]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59526113tert-butyl[(1-{[6-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridin-2-yl]methyl}-1H-1,2,3-triazol-4-yl)methyl]carbamate

Product 1

HCID 595256362-[(6-{[4-(Aminomethyl)-1H-1,2,3-triazol-1-yl]methyl}pyridin-2-yl)amino]-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of tert-butyl[(1-{[6-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridin-2-yl]methyl}-1H-1,2,3-triazol-4-yl)methyl]carbamate (90 mg, 0.15 mmol) in EtOAc (7.0 mL) at ° C. was added 4 M HCl in dioxane (1.88 mL, 7.50 mmol). The reaction was stirred at 0° C. for 4 h. The yellow suspension was quenched with saturated NaHCO3 and extracted with 5:1 CH2Cl2:MeOH (2×). The combined organic layers were dried (MgSO4), filtered, and evaporated. The residue was purified by reverse phase HPLC (15-75% MeCN/water w/0.025% TFA). Product fractions were neutralized with saturated NaHCO3, extracted with 5:1 CH2Cl2:MeOH (2×), dried (MgSO4), filtered, and evaporated to give the title compound as a yellow solid.

Workup

  1. customThe yellow suspension was quenched with saturated NaHCO3
  2. extractionextracted with 5:1 CH2Cl2
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by reverse phase HPLC (15-75% MeCN/water w/0.025% TFA)
  7. extractionextracted with 5:1 CH2Cl2
  8. dry with materialMeOH (2×), dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-a14c307c18c54eaaab3071077c94c454
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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