Diisopropylethylamine → (S)-N-(1-benzylpiperidin-3-yl)-N-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 919556Notes

Reaction equation

HRID 919556 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:24]=[CH:25][C:18]=12.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([N:14]([CH3:15])[C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:24]=[CH:25][C:18]=23)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57538111HCID 57538111, compoundHCID 66569260(S)-1-benzyl-N-methylpiperidin-3-amine

Product 1

HCID 86706438(S)-N-(1-benzylpiperidin-3-yl)-N-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 50.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-1-benzyl-N-methylpiperidin-3-amine (500 mg, 2.4 mmol) and 4-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine (697 mg, 2.4 mmol) in DMF (10 mL), DIEA (1.26 g, 9.7 mmol) was added and the reaction mixture was stirred at 60° C. overnight. After reaction was completed as indicated by TLC, the reaction mixture was diluted with EtOAc (40 mL) and was washed with water (3×20 mL). The EtOAc layer was then dried over Na2SO4 and evaporated in vacuo to give a residue that was purified by column chromatography (silica gel, gradient EtOAc in hexanes) to afford the titled intermediate (550 mg, 49%). 1H NMR (400 MHz, CD3OD): δ 8.26 (s, 1H), 8.15 (bs, 1H), 7.32 (m, 3H), 7.22 (m, 2H), 5.67 (s, 2H), 3.61 (t, J=9.2 Hz, 2H), 3.57 (m, 2H), 3.31 (s, 3H), 2.95 (m, 2H), 2.24 (m, 1H), 2.03 (m, 2H), 1.80 (m, 4H), 0.86 (m, 2H), 0.07 (s, 9H). LC-MS: m/z [M+1]=453.

Workup

  1. customAfter reaction
  2. washwas washed with water (3×20 mL)
  3. dry with materialThe EtOAc layer was then dried over Na2SO4
  4. customevaporated in vacuo
  5. customto give a residue that
  6. customwas purified by column chromatography (silica gel, gradient EtOAc in hexanes)

Sources & evidence

ORD record
ord-7c8c17dd7b16419d949a5ed4b1c88446
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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