2-Pyridinemethanamine → HCID 90386216, compound

HRID 2170198Notes

Reaction equation

HRID 2170198 reaction equation
Cl[C:2]1[C:7]2=[C:8]([Cl:11])[CH:9]=[CH:10][N:6]2[N:5]=[C:4]([CH:12]2[CH2:14][CH:13]2[C:15]#[N:16])[N:3]=1.[NH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][N:6]2[C:7]=1[C:2]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=[N:3][C:4]([CH:12]1[CH2:14][CH:13]1[C:15]#[N:16])=[N:5]2

Participants

5

Reactant 3

HCID 195092-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 90386161HCID 90386161, compound

Product 1

HCID 90386216HCID 90386216, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (±)-2-(4,5-dichloropyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (60.0 mg, 0.237 mmol) in THF (1 mL) was added 2-(aminomethyl)pyridine (0.0290 mL, 0.284 mmol) followed by DIPEA (0.124 mL, 0.711 mmol). The reaction mixture was stirred at RT for 1 hour. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (2×25 mL). The combined organic extracts was washed with brine (25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by CombiFlash (REDISEP®, silica gel, 4 g, 10% EtOAc/petroleum ether) to afford (±)-2-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (50.0 mg, 59.1%) as off-white solid. LCMS Condition B-41: retention time 0.67 min, [M+1]=325.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30-1.34 (m, 1H), 1.48-1.51 (m, 1H), 1.92-1.96 (m, 1H), 2.45-2.49 (m, 1H), 4.76 (t, J=4.8 Hz, 2H), 6.72 (d, J=2.8 Hz, 1H), 7.29 (q, J=4.8 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.68 (d, J=2.8 Hz, 1H), 7.77 (q, J=2.0 Hz, 1H), 8.14 (s, 1H), 8.53 (dd, J=1.2 Hz, J=3.2 Hz, 1H).

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined organic extracts was washed with brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by CombiFlash (REDISEP®, silica gel, 4 g, 10% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-e4c92fd3c6b7488baef2cc74d05ebc70
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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