Acetic Acid → 4-(8-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-6-ylethynyl)-1-(2,4,6-trifluoro-benzyl)-piperidin-4-ol

HRID 2242921Notes

Reaction equation

HRID 2242921 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([N:17]=[C:18]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)[CH:5]=[C:6]([C:8]#[C:9][C:10]2([OH:16])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[N:7]=1.[F:25][C:26]1[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[C:27]=1[CH:28]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl>[NH2:1][C:2]1[C:3]2[N:4]([N:17]=[C:18]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)[CH:5]=[C:6]([C:8]#[C:9][C:10]2([OH:16])[CH2:11][CH2:12][N:13]([CH2:28][C:27]3[C:26]([F:25])=[CH:33][C:32]([F:34])=[CH:31][C:30]=3[F:35])[CH2:14][CH2:15]2)[N:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5218452,4,6-TrifluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 685422064-(8-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-6-ylethynyl)-piperidin-4-ol

Product 1

HCID 685441444-(8-Amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-6-ylethynyl)-1-(2,4,6-trifluoro-benzyl)-piperidin-4-olYield 3.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(8-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-6-ylethynyl)-piperidin-4-ol (22 mg,0.068 mmol) and 2,4,6-trifluoro-benzaldehyde (11 mg, 0.068 mmol) in CH2Cl2 (2 mL) was added sodium triacetoxyborohydride (32 mg, 0.15 mmol) and acetic acid (6 uL, 0.10 mmol). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through a pad of silica-gel, washed with ethyl acetate. The eluant was concentrated. The residue was isolated by reversed phased HPLC eluting with a water/acetonitrile gradient to yield 4-(8-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-6-ylethynyl)-1-(2,4,6-trifluoro-benzyl)-piperidin-4-ol (1 mg, 3%). 1H NMR (300 MHz, DMSO): δ 7.92 (br s, 1H), 7.70 (m, 3H), 7.41 (s, 2H), 7.14 (s, 1H), 6.72 (s, 1H), 4.43 (s, 2H), 3.80 (m, 4H), 2.12-1.96 (m, 4 H). MS: m/z: 469 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of silica-gel
  2. washwashed with ethyl acetate
  3. concentrationThe eluant was concentrated
  4. customThe residue was isolated
  5. washby reversed phased HPLC eluting with a water/acetonitrile gradient

Sources & evidence

ORD record
ord-064c16ca18c54bcdb52763bcec05a926
Source dataset
uspto-grants-2010_03
Patent number
US07674791B2

Reaction notes

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