Diisopropylethylamine → US9433622, Dmx-131

HRID 55867

Reaction equation

HRID 55867 reaction equation
Cl[C:2]1[N:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:18]=[N:19][C:20]([CH2:23][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:21][CH:22]=3)[N:11]=2)=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH:31]1[CH2:35][CH2:34][CH2:33][CH:32]1[CH2:36][C:37]([NH2:39])=[O:38].CCN(C(C)C)C(C)C.CO.C(Cl)(Cl)Cl>CCO>[C:4]([C:3]1[C:2]([N:31]2[CH2:35][CH2:34][CH2:33][CH:32]2[CH2:36][C:37]([NH2:39])=[O:38])=[N:9][CH:8]=[C:7]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:18]=[N:19][C:20]([CH2:23][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:21][CH:22]=3)[N:11]=2)[CH:6]=1)#[N:5]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 21584188Chloroform methanolHCID 695393622-(Pyrrolidin-2-yl)acetamide hydrochlorideHCID 903695292-Chloro-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile

Product 1

HCID 90369534US9433622, Dmx-131

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of compound 18 (100 mg, 0.24 mmol) in EtOH (5 mL) was added 2-(pyrrolidin-2-yl)acetamide-HCl (160 mg, 1.22 mmol) and DIPEA (0.22 mL, 1.22 mmol) at rt and the reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to rt, concentrated to half of its volume and triturated with n-pentane, the precipitated solid was collected by filtration to obtain DMX-130 (80 mg, 65%) as a white solid. Rf: 0.4 (10% MeOH/CHCl3); (m/z): 499.8 [M+1]+; 1H NMR (300 MHz, DMSO-d6): δ 9.77 (1H, s), 9.13 (1H, d, J=2.4 Hz), 8.87 (1H, d, J=2.4 Hz), 8.66 (1H, d, J=1.8 Hz), 8.50 (1H, d, J=5.1 Hz), 8.16 (1H, dd, J=2.7, 9.0 Hz), 7.46 (1H, d, J=5.7 Hz), 7.38 (1H, d, J=9.0 Hz), 7.30 (1H, br), 6.84 (1H, br), 4.74 (1H, br), 3.97 (1H, br), 3.80-3.76 (1H, br), 3.59-3.53 (6H, m), 2.76-2.70 (1H, m), 2.40 (4H, br), 2.23-2.15 (1H, m), 2.10-2.98 (3H, m), 1.86-1.84 (1H, m).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. concentrationconcentrated to half of its volume
  4. customtriturated with n-pentane
  5. filtrationthe precipitated solid was collected by filtration
  6. customto obtain DMX-130 (80 mg, 65%) as a white solid

Sources & evidence

ORD record
ord-3168bd04921344eab3ba7adbb865797e
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Linked notes

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