Acetic Acid → HCID 178432170, compound

HRID 2282285Notes

Reaction equation

HRID 2282285 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]=O)=[CH:6][N:5]2[C:12]=1[C:13]1[S:14][C:15]([C:24]2[N:28]=[CH:27][N:26](C3CCCCO3)[N:25]=2)=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1.[NH2:35][CH2:36][CH2:37][NH:38][C:39](OC(C)(C)C)=O.C(Cl)Cl.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.FC(F)(F)C(O)=O>>[CH3:39][N:38]([CH2:10][C:7]1[CH:8]=[CH:9][C:4]2[N:5]([C:12]([C:13]3[S:14][C:15]([C:24]4[NH:28][CH:27]=[N:26][N:25]=4)=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=3)=[C:2]([CH3:1])[N:3]=2)[CH:6]=1)[CH2:37][CH2:36][NH2:35]

Participants

8

Reactant 7

HCID 176Acetic Acid2×HCID 712FormaldehydeHCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 187201N-BOC-ethylenediamineHCID 5049666Sodium triacetoxyborohydride2×HCID 58094904HCID 58094904, compound

Product 1

HCID 178432170HCID 178432170, compoundYield 14.1%

Procedure

The mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridine-6-carbaldehyde (0.0300 g, 0.0638 mmol) and N-(2-aminoethyl)(tert-butoxy)carboxamide (15.3 mg, 0.0956 mmol) in dry Methylene chloride (2.0 mL, 31 mmol) and Acetic acid (50 mg, 0.8 mmol) was stirred at r.t. for 20 min. Sodium triacetoxyborohydride (23.3 mg, 0.110 mmol) was added and the mixture was stirred at r.t. for 21 hours. Paraformaldehyde (25 mg, 0.28 mmol) was added, followed by Acetic acid (100 mg, 2 mmol). The mixture was stirred at r.t. for 10 min. Sodium triacetoxyborohydride (172 mg, 0.812 mmol) was added and the mixture was stirred at r.t. for 17 hours. The mixture was quenched with saturated NaHCO3, extracted with DCM. The DCM solution was washed with water, brine, dried over Na2SO4, filtered. The filtrate was chromatographed in a 24 g ISCO column using MeOH/DCM (0/100 to 5/95) to give a solid. LCMS: (FA) ES+ 629. This solid was treated with Trifluoroacetic Acid (1.0 mL, 13 mmol) in Methylene chloride (1.0 mL, 16 mmol) at r.t. for 18 hours. The mixture was rotavaped, azeotroped with DCM. The residue was triturated with Et2O and decanted to give a solid residue, dried in hi-vac to give 30 mg of crude product. HPLC purification gave a solid product (0.0040 g, 13.8% yield). LCMS: (FA) ES+ 445, ES− 443. 1H NMR (400 MHz, d4-methanol) δ 9.88 (s, 1H), 8.47 (s, 1H), 7.78-7.81 (m, 2H), 7.61 (s, 2H), 7.41-7.43 (m, 3H), 3.68 (s, 2H), 3.00-3.03 (m, 2H), 2.75 (s, 3H), 2.66-2.69 (m, 2H), 2.32 (s, 3H).

Workup

  1. stirringthe mixture was stirred at r.t. for 21 hours
  2. stirringThe mixture was stirred at r.t. for 10 min
  3. stirringthe mixture was stirred at r.t. for 17 hours
  4. customThe mixture was quenched with saturated NaHCO3
  5. extractionextracted with DCM
  6. washThe DCM solution was washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe filtrate was chromatographed in a 24 g ISCO column
  10. customto give a solid
  11. customazeotroped with DCM
  12. customThe residue was triturated with Et2O
  13. customdecanted
  14. customto give a solid residue
  15. customdried in hi-vac
  16. customto give 30 mg of crude product
  17. customHPLC purification

Sources & evidence

ORD record
ord-f5db6cf0f5a54764b8a262e24fab3d7f
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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