Hydrochloric Acid → N-(indan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

HRID 870557Notes

Reaction equation

HRID 870557 reaction equation
Cl.[CH2:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][C:16]=2[N:17]=1.COC(C)(C)C.O>O1CCCC1.C(OCC)(=O)C>[CH2:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[CH2:21][NH:20][CH2:19][CH2:18][C:16]=2[N:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 15413tert-Butyl methyl etherHCID 86726523tert-Butyl 2-((2,3-dihydro-1H-inden-2-yl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

Product 1

HCID 86726522N-(indan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amineYield 37%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Add portionwise hydrochloric acid (900 mL; 5M in water; 5.17 equiv; 4.50 mole; 1.08 kg) to a solution of tert-butyl 2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate (319 g; 1.00 equiv; 870.48 mmoles) in tetrahydrofuran (1.5 L). Once the addition is complete, stir the solution at 50° C. for 1 h. Cool the mixture to 25° C. and then add 3 L methyltert-butyl ether and 1 L water. Allow the solution to stand at 20° C. for 16 h. Separate the phases and extract the aqueous phase with dichloromethane (2 L). Discard the organic extracts and adjust the aqueous phase to pH 10 using 4M sodium hydroxide. Extract with ethyl acetate (3×3 L), and wash the combined organic extracts with saturated sodium chloride (2 L). Dry over anhydrous sodium sulfate, filter and concentrate to dryness to give a red gel. Redissolve the substance in ethyl acetate (300 mL) and petroleum ether (200 mL) at 50° C., and allow for precipitation over 24 hours. Filter and dry to afford the title compound (85 g, 37%). MS (m/z): 267 (M+1).

Workup

  1. additionOnce the addition
  2. temperatureCool the mixture to 25° C.
  3. waitto stand at 20° C. for 16 h
  4. customSeparate the phases
  5. extractionextract the aqueous phase with dichloromethane (2 L)
  6. extractionExtract with ethyl acetate (3×3 L)
  7. washwash the combined organic extracts with saturated sodium chloride (2 L)
  8. dry with materialDry over anhydrous sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate to dryness
  11. customto give a red gel
  12. custompetroleum ether (200 mL) at 50° C., and allow for precipitation over 24 hours
  13. filtrationFilter
  14. customdry

Sources & evidence

ORD record
ord-6c37db7237bc42c883da674117d258fe
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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