Dimethylformamide → HCID 57392676, compound

HRID 1262330Notes

Reaction equation

HRID 1262330 reaction equation
O[C:2]1[N:7]=[CH:6][C:5]2=[CH:8][CH:9]=[C:10]([C:11]3[C:12]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])=[N:13][CH:14]=[CH:15][CH:16]=3)[N:4]2[N:3]=1.CN(C)C=O.C(N(CC)C(C)C)(C)C.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.[NH2:58][C:59]1[CH:64]=[CH:63][C:62]([CH:65]2[CH2:70][CH2:69][N:68]([CH2:71][C:72]([NH2:74])=[O:73])[CH2:67][CH2:66]2)=[CH:61][CH:60]=1>>[CH3:21][S:18]([N:17]([CH3:22])[C:12]1[C:11]([C:10]2[N:4]3[C:5]([CH:6]=[N:7][C:2]([NH:58][C:59]4[CH:64]=[CH:63][C:62]([CH:65]5[CH2:66][CH2:67][N:68]([CH2:71][C:72]([NH2:74])=[O:73])[CH2:69][CH2:70]5)=[CH:61][CH:60]=4)=[N:3]3)=[CH:8][CH:9]=2)=[CH:16][CH:15]=[CH:14][N:13]=1)(=[O:20])=[O:19]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 142176Phenyl triflimideHCID 574161072-[4-(4-Aminophenyl)piperidin-1-yl]acetamideHCID 178482362HCID 178482362, compound

Product 1

HCID 57392676HCID 57392676, compoundYield 52%

Procedure

Into a 8-dram vial, N-[3-(2-Hydroxy-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-pyridin-2-yl]-N-methyl-methanesulfonamide (56 mg, 0.18 mmol), N,N-Dimethylformamide (0.50 mL, 6.4 mmol), N,N-Diisopropylethylamine (0.0672 mL, 0.386 mmol) and N-Phenylbis(trifluoromethanesulphonimide) (2.77 g, 7.75 mmol) were added. The reaction mixture was stirred at room temperature for 1 hour. 2-[4-(4-Amino-phenyl)-piperidin-1-yl]-acetamide (90.0 mg, 0.386 mmol) was added. The reaction was heated at 110° C. for 3 hours. The solvent was removed under vacuum overnight The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were combined and neutralized via polymer bound sulfonic acid column with 2N NH3 in methanol. The filtrate was concentrated to afford 2-[4-(4-{7-[2-(Methanesulfonyl-methyl-amino)-pyridin-3-yl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-phenyl)-piperidin-1-yl]-acetamide as a yellow solid (50 mg, 50%). LCMS (E/I+) 535.16 (M+H). NMR 1H (DMSO-d6)-9.42 (s, 1H), 9.01 (s, 1H), 8.56-8.61 (m, 2H), 7.64-7.69 (m, 1H), 7.56 (s, 1H), 7.54 (s, 1H), 7.19 (s, 1H), 7.07-7.14 (m, 2H), 6.98 (d, 2H, J=4.63 Hz), 3.13 (s, 3H), 3.00 (s, 3H), 2.84-2.96 (m, 4H), 2.32-2.44 (m, 1H), 2.08-2.19 (m, 2H), 1.64-176 (m, 4H).

Workup

  1. temperatureThe reaction was heated at 110° C. for 3 hours
  2. customThe solvent was removed under vacuum overnight The reaction mixture
  3. customwas purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-e17f6b18ed4149e5b569fa3d741ff7ab
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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