Acetic Acid → HCID 67147416, compound

HRID 2426603Notes

Reaction equation

HRID 2426603 reaction equation
Cl.Cl.C[O:4][C:5]([C:7]1[CH:12]=[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[N:10]=[C:9](Cl)[N:8]=1)=[O:6].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][C:23]=1[O:30][CH2:31][CH3:32].[C:33]([OH:36])(=[O:35])C.C(N(C(C)C)C(C)C)C.C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)C>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][N:17]2[CH2:18][CH2:19][CH:14]([NH:13][C:11]3[N:10]=[C:9]([C:33]([OH:36])=[O:35])[N:8]=[C:7]([C:5]([OH:4])=[O:6])[CH:12]=3)[CH2:15][CH2:16]2)=[CH:24][C:23]=1[O:30][CH2:31][CH3:32]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 547756424-Chloro-3-ethoxybenzaldehyde2×HCID 86618544HCID 86618544, compound2×

Product 1

HCID 67147416HCID 67147416, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
55 °C

Procedure

To a solution of 2-chloro-6-(piperidin-4-ylamino)-pyrimidine-4-carboxylic acid methyl ester dihydrochloride (51.6 mg, 0.15 mmol, 1.0 equiv; intermediate C5) in ethanol (2 mL) was added 4-chloro-3-ethoxy-benzaldehyde (33.2 mg, 0.18 mmol, 1.2 equiv; intermediate D2), acetic acid (27.0 mg, 0.45 mmol, 3.0 equiv) and N-ethyl diisopropylamine (58.3 mg, 0.45 mmol, 3.0 equiv) and the reaction mixture stirred at 55° C. After 1 h, sodium cyanoborohydride (47.1 mg, 0.75 mmol, 5.0 equiv), dissolved in ethanol (0.5 mL), was added and the mixture stirred at 55° C. After 8 h, a 10 M NaOH solution (0.75 mL) was added and heating continued at 55° C. over night. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 2.5 mg (4%) of the title compound. MS (ESI): 434.4 [M+H]+.

Workup

  1. additionwas added
  2. stirringthe mixture stirred at 55° C
  3. waitAfter 8 h
  4. temperatureheating
  5. waitcontinued at 55° C. over night
  6. customRemoval of the solvent
  7. customunder reduced pressure and purification by preparative HPLC on reversed phase
  8. washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-a0e1e11c79234a4a9862862f910bc931
Source dataset
uspto-grants-2011_06
Patent number
US07968568B2

Reaction notes

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