2-Pyridinemethanamine → Tert-butyl (1-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropyl)carbamate

HRID 2170179Notes

Reaction equation

HRID 2170179 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9](O)=[N:8][C:7]([C:12]1([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]1)=[N:6]2.F[P-](F)(F)(F)(F)F.[N:30]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=N1.C1CCN2C(=NCCC2)CC1.N1C=CC=CC=1CN>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([NH:32][CH2:33][C:38]1[CH:37]=[CH:36][CH:35]=[CH:34][N:30]=1)=[N:8][C:7]([C:12]1([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]1)=[N:6]2

Participants

6

Reactant 4

HCID 195092-PyridinemethanamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178452620HCID 178452620, compound

Product 1

HCID 90396872Tert-butyl (1-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropyl)carbamateYield 50.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of tert-butyl (1-(5-chloro-4-hydroxypyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropyl)carbamate (500 mg, 1.54 mmol) in acetonitrile (50 mL) was added BOP (1.02 g, 2.31 mmol), DBU (0.464 mL, 3.08 mmol) and the reaction mixture was stirred at RT for 1 h. Pyridin-2-ylmethanamine (166 mg, 1.54 mmol) was added to the reaction mixture and stirred for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed water (2×30 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash ISCO (REDISEP®, SiO2, 12 g, 10% MeOH/CHCl3) to give tert-butyl (1-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropyl)carbamate (320 mg, 50.1%) as a pale yellow solid. LCMS Condition B-16: retention time 1.06 min, [M+1]=415.2. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.89-0.92 (m, 2H), 1.15-1.17 (m, 2H), 1.38 (s, 9H), 4.75 (d, J=5.7 Hz, 2H), 6.69 (d, J=2.7 Hz, 1H), 7.25-7.33 (m, 3H), 7.52-7.56 (m, 1H), 7.73-7.76 (m, 1H), 7.96-7.98 (m, 1H), 8.53 (d, J=5.2 Hz, 1H).

Workup

  1. stirringstirred for 12 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwashed water (2×30 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by CombiFlash ISCO (REDISEP®, SiO2, 12 g, 10% MeOH/CHCl3)

Sources & evidence

ORD record
ord-cebdc733c2094b39ad1b1b703ce63b2e
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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