Pyridine → HCID 90386145, compound

HRID 2170182Notes

Reaction equation

HRID 2170182 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.[C:34](Cl)(=[O:36])[CH3:35]>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][C:34](=[O:36])[CH3:35])[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 6367Acetyl chlorideHCID 90386182HCID 90386182, compound

Product 1

HCID 90386145HCID 90386145, compoundYield 37.3%

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 acetyl chloride (0.0140 mL, 0.202 mmol) and the reaction mixture 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 combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-111 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)acetamide (25.0 mg, 37.3%) as white solid. LCMS Condition B-34: retention time 2.14 min, [M+1]=399.0. HPLC Condition B-31: retention time 6.09 min, Purity 99.83%. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.93-1.01 (m, 2H), 1.35-1.41 (m, 2H), 1.85 (s, 3H), 4.68 (d, J=4.8 Hz, 2H), 6.68 (d, J=2.7 Hz, 1H), 6.99 (t, J=4.9 Hz, 1H), 7.27 (dd, J=6.5 Hz, J=4.9 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.40-7.48 (m, 1H), 7.48-7.57 (m, 4H), 7.67 (d, J=2.7 Hz, 1H), 7.76 (td, J=7.7 Hz, J=1.7 Hz, 1H), 8.37-8.41 (m, 1H), 8.44 (s, 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. dry with materialThe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Condition B-111 as described in general methods)

Sources & evidence

ORD record
ord-ab38a2267b2e42a89bc3f06ac5b363b4
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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