Pyridine → HCID 90386153, compound

HRID 2170183Notes

Reaction equation

HRID 2170183 reaction equation
[NH2:1][C:2]1([C:5]2[N:10]=[C:9]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:8]3=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:20]=[CH:21][N:7]3[N:6]=2)[CH2:4][CH2:3]1.N1C=CC=CC=1.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C(Cl)Cl>[C:22]1([C:19]2[CH:20]=[CH:21][N:7]3[C:8]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[N:10][C:5]([C:2]2([NH:1][S:35]([CH3:34])(=[O:37])=[O:36])[CH2:3][CH2:4]2)=[N:6]3)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 90386182HCID 90386182, compound

Product 1

HCID 90386153HCID 90386153, compoundYield 35.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(1-aminocyclopropyl)-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (60.0 mg, 0.168 mmol)) in DCM (15 mL) was added pyridine (0.0200 mL, 0.253 mmol) followed by methanesulfonylchloride (0.0200 mL, 0.253 mmol) and the reaction stirred at RT for 2 h then concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed with water (2×30 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-94 as described in general methods) to give N-(1-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropyl)methanesulfonamide (26.0 mg, 35.5%) as white solid. LCMS Condition B-34: retention time 2.32 min, [M+1]=435.0. HPLC Condition B-31: retention time 7.72 min, Purity 99.61%. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25-1.31 (m, 2H), 1.36-1.42 (m, 2H), 2.99 (s, 3H), 4.71 (d, J=4.8 Hz, 2H), 6.71 (d, J=2.7 Hz, 1H), 7.07 (t, J=4.8 Hz, 1H), 7.27 (ddd, J=6.8 Hz, J=5.5 Hz, J=1.0 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.41-7.45 (m, 1H), 7.47-7.57 (m, 4H), 7.72-7.77 (m, 2H), 8.06 (s, 1H), 8.35-8.40 (m, 1H).

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with water (2×30 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC (Condition B-94 as described in general methods)

Sources & evidence

ORD record
ord-6bf6c29c402d47a2b3aa9ad73cd3d915
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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