Isopropylamine → HCID 131731382, compound

HRID 1021292Notes

Reaction equation

HRID 1021292 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:42])=[C:12]([C:16]2[CH:17]=[N:18][C:19]([O:22][CH2:23][CH:24]3[CH2:29][CH2:28][N:27](C(OC4C=CC([N+]([O-])=O)=CC=4)=O)[CH2:26][CH2:25]3)=[N:20][CH:21]=2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[CH:43]([NH2:46])([CH3:45])[CH3:44].CN1[C:52](=[O:53])[CH2:51]CC1>>[F:42][C:11]1[C:10]([CH2:9][OH:8])=[CH:15][CH:14]=[CH:13][C:12]=1[C:16]1[CH:17]=[N:18][C:19]([O:22][CH2:23][CH:24]2[CH2:29][CH2:28][N:27]([CH2:51][C:52]([NH:46][CH:43]([CH3:45])[CH3:44])=[O:53])[CH2:26][CH2:25]2)=[N:20][CH:21]=1

Participants

4

Reactant 3

HCID 6363Isopropylamine3×HCID 13387N-methyl-2-pyrrolidoneHCID 89600734HCID 89600734, compound

Product 1

HCID 131731382HCID 131731382, compound

Conditions

Temperature
70 °C

Procedure

4-Nitrophenyl 4-[({5-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]pyrimidin-2-yl}oxy)methyl]piperidine-1-carboxylate (200 mg) was mixed with NMP (5 ml), and isopropyl amine (0.3 ml) was added thereto, followed by stirring at 70° C. for 6 hours. iPrNH2 (0.3 ml) was added to the reaction mixture, followed by stirring at 70° C. overnight. iPrNH2 (0.4 ml) was added to the reaction mixture, followed by stirring at 70° C. for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, and then a 1 M aqueous NaOH solution and EtOAc were added thereto. The organic layer was concentrated under reduced pressure. The obtained residue was mixed with THF (4 ml), and a 1 M TBAF/THF solution (0.7 ml) was added thereto, followed by stirring at room temperature for 2 hours. EtOAc and water were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/hexane/MeOH/CHCl3) to obtain 4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]-N-isopropylpiperidine-1-carboxyamide (107.4 mg).

Workup

  1. additionwas added
  2. stirringby stirring at 70° C. overnight
  3. stirringby stirring at 70° C. for 3 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationconcentrated under reduced pressure
  6. additiona 1 M aqueous NaOH solution and EtOAc were added
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. additionThe obtained residue was mixed with THF (4 ml)
  9. additiona 1 M TBAF/THF solution (0.7 ml) was added
  10. stirringby stirring at room temperature for 2 hours
  11. additionEtOAc and water were added to the reaction mixture
  12. dry with materialthe organic layer was dried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (EtOAc/hexane/MeOH/CHCl3)

Sources & evidence

ORD record
ord-759aa366fd8d45cf81ee1b0f82d3cc9b
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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