Hydrochloric Acid → N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate

HRID 870566Notes

Reaction equation

HRID 870566 reaction equation
[ClH:1].[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[CH2:20][N:19](C(OC(C)(C)C)=[O:22])[CH2:18][C:16]=2[N:17]=1>O1CCCC1.O.C(OC)(C)(C)C>[OH2:22].[ClH:1].[ClH:1].[CH2:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:2][CH:3]1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[CH2:20][NH:19][CH2:18][C:16]=2[N:17]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 86726530tert-butyl-2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate

Product 1

HCID 86726534N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrateYield 80.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

Charge 670 mL of 5 M hydrochloric acid (3.35 mol) to a solution of tert-butyl 2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H pyrrolo[3,4-d]pyrimidine-6-carboxylate (226 g, 641.25 mmol) in tetrahydrofuran (2.0 L) at 17° C., maintaining the internal temperature below 26° C. during the addition. Heat the resulting solution to 50° C. for 16 h, cool to 25° C. and dilute with 500 mL of water and 500 mL of tert-butylmethylether. Separate the resulting layers and extract with tert-butylmethylether (3×1 L). Concentrate the water phase down to a reaction volume of ca. 200 mL, and filter the resulting slurry. Rinse the cake with tert-butylmethylether (2×200 mL) and dry to give the title product (177 g, 80%) as a light brown solid. MS (m/z): 253.2 (M−2HCl—H2O+1).

Workup

  1. temperaturemaintaining the internal temperature below 26° C.
  2. additionduring the addition
  3. temperaturecool to 25° C.
  4. customSeparate the resulting layers
  5. extractionextract with tert-butylmethylether (3×1 L)
  6. concentrationConcentrate the water phase down to a reaction volume of ca. 200 mL
  7. filtrationfilter the resulting slurry
  8. washRinse the cake with tert-butylmethylether (2×200 mL)
  9. customdry

Sources & evidence

ORD record
ord-0285cd0583574258ac95a9abb35d0d9c
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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