Diisopropylethylamine → HCID 86671079, compound

HRID 1485573Notes

Reaction equation

HRID 1485573 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:12]=[CH:13][C:14]2[N:15]=[CH:16][N:17]=[C:18](OC3CCOCC3)[C:19]=2[N:20]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>O1CCOCC1>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]2[N:15]=[CH:16][N:17]=[C:18]([NH:41][CH:38]3[CH2:37][CH2:36][N:35]([C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])[CH2:40][CH2:39]3)[C:19]=2[N:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 86671079HCID 86671079, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Hunig's base (6.53 mL, 37.5 mmol) was added to a suspension of 4,6-dichloropyrido[3,2-d]pyrimidine (intermediate 1, 5.00 g, 25.0 mmol) and tert-butyl-4-aminopiperidine-1-carboxylate (6.00 g, 30.0 mmol) in 1,4-dioxane (250 mL) at room temperature. The reaction mixture was refluxed for 1 h, and cooled to room temperature. The solvent was removed under reduced pressure, EtOAc and water were poured into the residue, and the separated aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc) to give a pale yellow solid which was washed with MeOH afforded tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-ylamino)piperidine-1-carboxylate (8.72 g, 96%) as a off white solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.49 (9H, s), 1.50-1.62 (2H, m), 2.10-2.15 (2H, m), 2.98-3.01 (2H, m), 4.01-4.25 (2H, m), 4.25-4.40 (1H, m), 6.86 (1H, d, J=7.6 Hz), 7.62 (1H, d, J=8.8 Hz), 8.04 (1H, d, J=8.8 Hz), 8.62 (1H, s).

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. customThe solvent was removed under reduced pressure, EtOAc and water
  3. additionwere poured into the residue
  4. extractionthe separated aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (EtOAc)
  10. customto give a pale yellow solid which
  11. washwas washed with MeOH

Sources & evidence

ORD record
ord-1f3b863164e84b1badb4da769aa0772f
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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