Diisopropylethylamine → N4-(1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydroquinolin-3-yl)-N4-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine

HRID 2389542Notes

Reaction equation

HRID 2389542 reaction equation
OC(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]([NH:23][CH3:24])[CH2:14]1.Cl[C:30]1[N:35]=[C:34]([NH2:36])[N:33]=[C:32]2[NH:37][N:38]=[CH:39][C:31]=12.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O.O>[Cl:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:12][N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]([N:23]([CH3:24])[C:30]2[N:35]=[C:34]([NH2:36])[N:33]=[C:32]3[NH:37][N:38]=[CH:39][C:31]=23)[CH2:14]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 117896254-chloro-1H-pyrazolo[3,4-d]pyrimidin-6-amineHCID 86643199HCID 86643199, compound

Product 1

HCID 59400259N4-(1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydroquinolin-3-yl)-N4-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamineYield 59.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 1-(3,4-dichlorobenzyl)-N-methyl-1,2,3,4-tetrahydroquinolin-3-amine TFA salt (200 mg, 0.52 mmol) and 4-chloro-1H-pyrazolo[3,4-d]pyrimidin-6-amine (211 mg, 1.24 mmol) in dimethylacetamide (5 mL) was treated with diisopropylethylamine (0.327 ml, 3.5 eq). The mixture was heated at 120° C. for 22 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with water and dried. The residue was purified by flash column (eluted with ethyl acetate:hexane: 1:1 to 100% ethyl acetate) to give N4-(1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydroquinolin-3-yl)-N4-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine as a cream solid (140 mg). 1H NMR (DMSO) 400 MHz δ 12.52 (s, 1H), 7.84 (br, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.52 (d, J=2.0 Hz, 1H), 7.27 (dd, J=2.0 Hz and 8.4 Hz, 1H), 7.13 (brs, 1H), 6.98 (d, J=6.8 Hz, 1H), 6.94 (t, J=7.2 Hz, 1H), 6.55 (t, J=7.2 Hz, 1H), 6.49 (d, J=8.4 Hz, 1H), 6.0 (brs, 2H), 5.48 (br, 1H), 4.51 (dd, J=17.2 Hz and 58.0 Hz, 2H), 3.59 (t, J=10.4 Hz, 1H), 3.30 (m, 1H), 3.18 (s, 3H), 2.79 (m, 1H). LCMS m/e 455 (M+H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water
  5. customdried
  6. customThe residue was purified by flash column (eluted with ethyl acetate:hexane: 1:1 to 100% ethyl acetate)

Sources & evidence

ORD record
ord-091ef9d9e364455e86d89c2050b79590
Source dataset
uspto-grants-2012_09
Patent number
US08273754B2

Reaction notes

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