Acetic Acid → 4-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550811Notes

Reaction equation

HRID 550811 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1.C(N(CC)C(C)C)(C)C.C(O)(=O)C.[F:35][C:36]([F:46])([F:45])[C:37]1[CH:38]=[C:39]([CH:42]=[CH:43][CH:44]=1)[CH:40]=O.C([BH3-])#N.[Na+]>CO>[CH3:2][O:3][C:4]1[C:5]2[N:12]=[C:11]([NH:13][C:14]([N:16]3[CH2:17][CH2:18][N:19]([CH2:40][C:39]4[CH:42]=[CH:43][CH:44]=[C:37]([C:36]([F:35])([F:45])[F:46])[CH:38]=4)[CH2:20][CH2:21]3)=[O:15])[S:10][C:6]=2[N:7]=[CH:8][N:9]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 679903-(Trifluoromethyl)benzaldehydeHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 86616506Piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride

Product 1

HCID 248306124-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amideYield 58%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (2 g, 6.0 mmol) in methanol (200 mL) was treated with N,N-diisopropylethylamine (2.2 mL, 12.6 mmol). The mixture was stirred at 25° C. for 10 min until a clear solution formed. At this time, the reaction was treated with acetic acid (1.75 mL, 30.6 mmol), 3-trifluoromethy-benzaldehyde (2.4 mL, 17.9 mmol) and sodium cyanoborohydride (1.1 g, 17.7 mmol). This mixture was stirred at 25° C. overnight. The reaction was then concentrated in vacuo and partitioned between methylene chloride and an aqueous phosphate buffer (pH=7). The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo to give a solid. This solid was dissolved in methanol and absorbed onto silica gel (4 g). ISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride) afforded 4-(3-trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (1.56 g, 58%) as a white solid; LRMS for C19H19F3N6O2S (M+H)+ at m/z=453. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. customformed
  2. stirringThis mixture was stirred at 25° C. overnight
  3. concentrationThe reaction was then concentrated in vacuo
  4. custompartitioned between methylene chloride
  5. washThe organics were washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a solid
  10. customabsorbed onto silica gel (4 g)
  11. washISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride)

Sources & evidence

ORD record
ord-1aa714d8ba5d40d0ac2a3bc9b3aedbfb
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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