Acetic Acid → HCID 67496521, compound

HRID 1628276Notes

Reaction equation

HRID 1628276 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:32])[C@@H:16]([NH:24]C(=O)OC(C)(C)C)[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1.Cl.O1CCOCC1.[S:40]1[CH:44]=[C:43]([CH:45]=O)[N:42]=[CH:41]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:32])[C@@H:16]([NH:24][CH2:45][C:43]3[N:42]=[CH:41][S:40][CH:44]=3)[CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 70865451HCID 70865451, compound

Product 1

HCID 67496521HCID 67496521, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (S)-1-(3-(2-aminopyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (36.C) (200 mg, 0.46 mmol) in THF (2 mL) was added 4M HCl in dioxane (2 mL, 8 mmol). The mixture was stirred at room temperature for 2 hours and then was concentrated. The residue was neutralized with saturated aqueous NaHCO3 and extracted with 4:1 DCM/isopropanol. The organic layers were combined, washed with brine, dried on MgSO4 and concentrated. The residue was dissolved in DCM and then thiazole-4-carbaldehyde (56 mg, 0.50 mmol) was added. The mixture was stirred for 1 h at room temperature at which time acetic acid (28 μL, 0.46 mmol) and sodium triacetoxyborohydride (293 mg, 1.38 mmol) were added. The mixture was stirred at room temperature for additional 2 hours, concentrated and the residue purified by reverse phase preparative HPLC to afford (2S)—N-(3-(2-aminopyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide 36 (58 mg, 29% yield) as a white solid. LCMS ESI (pos.) m/e: 430.1 (M+1): 1H NMR (400 MHz, MeOH-D4) δ ppm 9.12 (d, J=1.96 Hz, 1H), 7.91-7.97 (m, 2H), 7.79 (d, J=1.96 Hz, 1H), 7.42-7.57 (m, 3H), 7.25-7.36 (m, 5H), 7.18-7.21 (m, 1H), 7.13-7.17 (m, 1H), 4.42-4.54 (m, 2H), 4.25 (dd, J=9.39, 5.87 Hz, 1H), 3.42 (dd, J=13.30, 5.87 Hz, 1H), 3.25 (dd, J=13.30, 9.00 Hz, 1H).

Workup

  1. concentrationwas concentrated
  2. extractionextracted with 4:1 DCM/isopropanol
  3. washwashed with brine
  4. customdried on MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in DCM
  7. additionwere added
  8. stirringThe mixture was stirred at room temperature for additional 2 hours
  9. concentrationconcentrated
  10. customthe residue purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-e399628418274b229ae3d3b1f022ea25
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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