Water → tert-butyl-2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate

HRID 870565Notes

Reaction equation

HRID 870565 reaction equation
C(N(C(C)C)C(C)C)C.Cl[C:11]1[N:12]=[CH:13][C:14]2[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17][C:15]=2[N:16]=1.[CH2:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH:28]1[NH2:36].O>CN1CCCC1=O>[C:23]([O:22][C:20]([N:18]1[CH2:19][C:14]2[CH:13]=[N:12][C:11]([NH:36][CH:28]3[CH2:29][C:30]4[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH2:27]3)=[N:16][C:15]=2[CH2:17]1)=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 962WaterHCID 763102-AminoindaneHCID 81531DiisopropylethylamineHCID 66570699tert-butyl 2-chloro-5H,6H,7H-pyrrolo(3,4-d)pyrimidine-6-carboxylate

Product 1

HCID 86726530tert-butyl-2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Charge 450 mL (2.58 mol) of N-ethyl-N-isopropylpropan-2-amine into a 15° C. solution of tert-butyl 2-chloro-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate (220 g, 860.37 mmol) and 2,3-dihydro-1H-inden-2-amine (137.7 g, 1.03 mol) in 1-methylpyrrolidin-2-one (3.6 L). Heat the resulting mixture to 80° C. for 16 h, then cool to 30° C. and transfer the resulting mixture into 5 L of water at 25° C. Filter the resulting solid and rinse the filter cake with water (2×300 mL). Reslurry the solid in ethyl acetate (350 mL) for 45 min at 15° C. Filter the slurry, rinsing with 15° C. ethyl acetate (2×250 mL), and dry to give the title compound (226 g, 75%) as an off-white solid. 1H NMR (d6-DMSO) 1.45 (s, 9H), 2.87 (dd, J=7.2, 15.8 Hz, 2H), 3.24 (dd, J=7.2, 15.8 Hz, 2H), 4.36 (d, 10.4 Hz, 2H), 4.44 (d, J=12.8 Hz, 2H), 4.60 (m, 1H), 7.14 (m, 2H), 7.20 (m, 2H), 7.55 (d, J=6.8 Hz, 1H), 8.27 (d, J=7.2 Hz, 1H).

Workup

  1. temperaturecool to 30° C.
  2. customat 25° C
  3. filtrationFilter the resulting solid
  4. washrinse the filter cake with water (2×300 mL)
  5. customfor 45 min
  6. customat 15° C
  7. filtrationFilter the slurry
  8. washrinsing with 15° C. ethyl acetate (2×250 mL)
  9. customdry

Sources & evidence

ORD record
ord-3bfbe551c9a34dd7958c72d2bc5778ab
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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