Diisopropylethylamine → (R)-N-(1-benzylpiperidin-3-yl)-N-methyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 919563Notes

Reaction equation

HRID 919563 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[C:18]2[CH:25]=[CH:24][N:23]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:19]=2[N:20]=[CH:21][N:22]=1.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[C:18]3[CH:25]=[CH:24][N:23]([S:26]([C:29]4[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=4)(=[O:28])=[O:27])[C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 442289674-Chloro-7-(p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 59418231(3R)-N-Methyl-1-(phenylmethyl)-3-piperidinamine

Product 1

HCID 86706441(R)-N-(1-benzylpiperidin-3-yl)-N-methyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 40.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-1-benzyl-N-methylpiperidin-3-amine (800 mg, 3.9 mmol) and 4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (1.2 g, 3.9 mmol) in DMF (10 mL), DIEA (2.02 mL, 15.6 mmol) was added and the reaction mixture was stirred at 60° C. overnight. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with EtOAc (100 mL) and was washed with water (3×40 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 (750 mg, 40%). 1H-NMR (400 MHz, CDCl3): δ 8.37 (s, 1H), 8.02 (d, J=8.4 Hz, 2H), 7.38 (d, 0.1=4.0 Hz, 1H), 7.28 (m, 7H), 6.53 (d, J=3.6 Hz, 1H), 3.59 (d, J=13.2 Hz, 1H), 3.46 (d, J=13.2 Hz, 1H), 3.13 (s, 3H), 2.89 (m, 2H), 2.37 (s, 3H), 2.09 (t, J=10.8 Hz, 1H), 1.96 (dt, J=1.2, 10.8 Hz, 1H), 1.83 (m, 2H), 1.65 (m, 3H). LC-MS: m/z [M+1]=476.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. washwas washed with water (3×40 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-0695c17a349b4807b3e831d8957c19e3
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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