Hydrochloric Acid → (S)-6-(3-aminopiperidin-1-yl)pyrido[3,2-d]pyrimidin-4-amine

HRID 1049926Notes

Reaction equation

HRID 1049926 reaction equation
[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18]C(=O)OC(C)(C)C)[CH2:13]3)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.O1CCOCC1>CO>[NH2:18][C@H:14]1[CH2:15][CH2:16][CH2:17][N:12]([C:10]2[CH:9]=[CH:8][C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[N:11]=2)[CH2:13]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86703922tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate

Product 1

HCID 86703923(S)-6-(3-aminopiperidin-1-yl)pyrido[3,2-d]pyrimidin-4-amineYield 107.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 40 mL screw-cap vial was added tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate 43 (2.53 g, 7.35 mmol) followed by methanol (7 mL), then HCl in dioxane (4 mol/L, 7.5 equiv., 55.1 mmol, 13.8 mL). The reaction was stirred at room temperature for 2 hours. Resulting precipitate was collected by filtration, and washed 2× with ethyl acetate, yielding 1.93 g of product as an orange solid, 3×HCl salt. 25 mg was purified by reverse phase HPLC, yielding 5 mg of neutralized product. 1H NMR (400 MHz, DMSO) δ 8.17-8.13 (s, 1H), 7.77-7.73 (d, J=9.3 Hz, 1H), 7.46-7.39 (d, J=9.4 Hz, 1H), 7.39-7.07 (s, 2H), 4.48-4.26 (m, 2H), 3.03-2.90 (m, 1H), 2.73-2.62 (m, 2H), 1.93-1.82 (m, 1H), 1.82-1.67 (m, 1H), 1.52-1.36 (m, 1H), 1.34-1.16 (m, 1H). LCMS M?Z (M+H)=245.

Workup

  1. customTo a 40 mL screw-cap vial
  2. customResulting precipitate
  3. filtrationwas collected by filtration
  4. washwashed 2× with ethyl acetate

Sources & evidence

ORD record
ord-a355f39b518649cc86ce8650ffe0f89c
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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