Triethylamine → (S)-4-Amino-6-((1-(1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 75288

Reaction equation

HRID 75288 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[N:6][C:7]([C@@H:17]([NH2:19])[CH3:18])=[C:8]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:9]=2)[CH:4]=[CH:3]1.Cl[C:21]1[C:26]([C:27]#[N:28])=[C:25](Cl)[N:24]=[C:23]([S:30][CH3:31])[N:22]=1.CC[N:34](CC)CC>C1COCC1.CCOC(C)=O>[NH2:34][C:21]1[C:26]([C:27]#[N:28])=[C:25]([NH:19][C@H:17]([C:7]2[N:6]=[C:5]3[CH:4]=[CH:3][N:2]([CH3:1])[C:10]3=[CH:9][C:8]=2[N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[CH3:18])[N:24]=[C:23]([S:30][CH3:31])[N:22]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 42016204,6-Dichloro-2-(methylsulfanyl)pyrimidine-5-carbonitrileHCID 86707976(S)-1-(1-Methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 86707979(S)-4-Amino-6-((1-(1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-2-(methylthio)pyrimidine-5-carbonitrileYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(1-Methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (200 mg, 0.768 mmol) was dissolved in THF (5 mL) along with 4,6-dichloro-2-(methylthio)pyrimidine-5-carbonitrile (169 mg, 0.768 mmol) and Et3N (0.118 mL, 0.845 mmol) to give an orange suspension. The reaction mixture was stirred at room temperature for 2 h, then diluted with EtOAc and washed aq 1M HCl (3×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was then loaded onto an ISCO® silica gel cartridge (12 g) and eluted using an EtOAc/Hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white solid (117 mg, 61%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36-1.50 (m, 3 H), 2.43-2.47 (m, 3 H), 2.72-2.88 (m, 2 H), 2.99-3.15 (m, 2 H), 3.68-3.89 (m, 7 H), 5.89-6.02 (m, 1 H), 6.46-6.58 (m, 1 H), 7.04-7.18 (m, 1 H), 7.21-7.42 (m, 2 H), 7.53-7.65 (m, 1 H), 7.82-7.95 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H24N8OS, 425.5; found 425.5.

Workup

  1. customto give an orange suspension
  2. washwashed aq 1M HCl (3×15 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washeluted
  7. customThe product was collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8f1cf9110a8a47e7b739f8c32b634ae3
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Linked notes

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