Triethylamine → tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate

HRID 1049925Notes

Reaction equation

HRID 1049925 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH2:12])[C:10]=2[N:11]=1.[NH:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14]1.C(N(CC)CC)C>CC(N(C)C)=O>[NH2:12][C:9]1[C:10]2[N:11]=[C:2]([N:13]3[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:14]3)[CH:3]=[CH:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 867038966-Chloropyrido[3,2-d]pyrimidin-4-amine

Product 1

HCID 86703922tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamateYield 66.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To 40 mL screw-cap vials was added 6-chloropyrido[3,2-d]pyrimidin-4-amine (2.00 g, 11.1 mmol) followed by tert-butyl N-[(3S)-3-piperidyl]carbamate (1.1 equiv., 12.2 mmol, 2.44 g) then dimethylacetamide (10 mL) and triethylamine (3 equiv., 33.2 mmol, 4.65 mL). The reaction was capped and shaken at 100° C. for 42 h, then an additional 24 h at 115° C. The reaction was cooled to room temperature, then partitioned with ethyl acetate:water. Residual chloride starting material was removed by filtration. The filtrate phases were separated, and the organics dried over sodium sulfate, filtered and concentrated, yielding 2.53 g of product. 1H NMR (400 MHz, DMSO) δ 8.19-8.13 (s, 1H), 7.81-7.74 (d, J=9.3 Hz, 1H), 7.43-7.39 (d, J=9.1 Hz, 1H), 6.95-6.85 (d, J=6.6 Hz, 1H), 4.32-4.19 (m, 2H), 3.50-3.38 (m, 1H), 3.19-3.04 (m, 1H), 2.96-2.85 (m, 1H), 1.90-1.80 (m, 1H), 1.80-1.67 (m, 1H), 1.60-1.34 (m, 11H). LCMS M/Z (M+H)=345.

Workup

  1. customTo 40 mL screw-cap vials
  2. customThe reaction was capped
  3. customan additional 24 h
  4. customat 115° C
  5. temperatureThe reaction was cooled to room temperature
  6. custompartitioned with ethyl acetate
  7. customResidual chloride starting material was removed by filtration
  8. customThe filtrate phases were separated
  9. dry with materialthe organics dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-8b03d9613a6f44029575e246f93cb55e
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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