4-Fluoroaniline → HCID 86624701, compound

HRID 604916Notes

Reaction equation

HRID 604916 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([NH:23][C:24]2[S:25][C:26]([CH:29]=O)=[CH:27][N:28]=2)[CH:14]=[CH:15][C:16]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O1CCCC1.C(O)(=O)C>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH2:29][C:26]2[S:25][C:24]([NH:23][C:13]3[CH:14]=[CH:15][C:16]([N:17]4[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]4)=[C:11]([O:10][CH3:9])[CH:12]=3)=[N:28][CH:27]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 97314-Fluoroaniline2×HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 86624700HCID 86624700, compound

Product 1

HCID 86624701HCID 86624701, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

21 mg (0.19 mmol) 4-Fluoroaniline was dissolved in tetrahydrofurane (1 ml). 65 mg (0.21 mmol) 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazole-5-carbaldehyde was added. The suspension was stirred at room temperature for 10 minutes. 133 mg (0.56 mmol) sodium triacetoxyborohydride and 23 mg (0.38 mmol) acetic acid were added and the reaction was stirred at room temperature over night. Since the reaction was not complete the same amount of 4-fluoroaniline, sodium triacetoxyborohydride and acetic acid were added and the reaction stirred at room temperature over night. 2N aqueous NaOH solution was added and the reaction was extracted once with methylene chloride. The organic layer was washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified on silica gel with ethyl acetate yielding 22 mg (26%) [5-(4-fluoro-benzyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a light yellow solid. MS ISP (m/e): 410.1 (100) (M+H)+. 1H NMR (CDCl3, 250 MHz): δ (ppm)=7.63 (s, 1H), 7.28-7.16 (m, 4H), 6.95-6.87 (m, 4H), 6.66-6.60 (m, 2H), 4.39 (s, 2H), 3.85 (s, 3H), 2.29 (s, 3H).

Workup

  1. stirringthe reaction was stirred at room temperature over night
  2. additionwere added
  3. stirringthe reaction stirred at room temperature over night
  4. extractionthe reaction was extracted once with methylene chloride
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe crude product was purified on silica gel with ethyl acetate yielding 22 mg (26%) [5-(4-fluoro-benzyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a light yellow solid

Sources & evidence

ORD record
ord-1bb573e525994939b9e6153ef75ca75b
Source dataset
uspto-grants-2011_03
Patent number
US07910740B2

Reaction notes

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