2-Methoxyethanol → N-tert-Butyl-3-(2-{4-[4-((R)-2-hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide

HRID 1262033Notes

Reaction equation

HRID 1262033 reaction equation
[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21](S(C)=O)=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[NH2:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]2[CH2:48][CH2:47][N:46]([CH2:49][C@H:50]([OH:52])[CH3:51])[CH2:45][CH2:44]2)=[CH:39][CH:38]=1.COCCO>>[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21]([NH:36][C:37]4[CH:38]=[CH:39][C:40]([N:43]5[CH2:44][CH2:45][N:46]([CH2:49][C@H:50]([OH:52])[CH3:51])[CH2:47][CH2:48]5)=[CH:41][CH:42]=4)=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 80192-MethoxyethanolHCID 81531DiisopropylethylamineHCID 28408103(2R)-1-[4-(4-Aminophenyl)piperazin-1-yl]propan-2-olHCID 66711063N-tert-Butyl-3-(2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide

Product 1

HCID 66711258N-tert-Butyl-3-(2-{4-[4-((R)-2-hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamideYield 60%

Procedure

N-tert-Butyl-3-(2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide (125.1 mg, 0.0003187 mol), N,N-Diisopropylethylamine (0.1665 mL, 0.0009561 mol) and (R)-1-[4-(4-Amino-phenyl)-piperazin-1-yl]-propan-2-ol (150 mg, 0.00064 mol) were dissolved in 2-Methoxyethanol (2.24 mL, 0.0284 mol) and the reaction was irradiated at 300 watts, 180° C. for 40 minutes or until HPLC showed consumption of starting material. The reaction mixture was then reduced en vacuo and the product was isolated and purified by Gilson prep HPLC to afford 107.72 mg of N-tert-Butyl-3-(2-{4-[4-((R)-2-hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide as a lyophilized powder. (M+H)=564.2. 1H NMR (400 MHz, DMSO, d6) δ 9.38 (s, 1H), 9.01 (s, 1H), 8.56 (s, 1H), 8.35 (d, 1H, J=7.92 Hz), 7.85 (d, 1H, J=8.12 Hz), 7.73 (m, 1H), 7.66 (d, 2H, J=9.00 Hz), 7.60 (s, 1H), 7.18 (d, 1H, J=4.76 Hz), 7.02 (d, 2H, J=9.01 Hz), 6.97 (d, 1H, J=4.76 Hz), 4.13 (m, 1H), 3.61 (m, 5H), 3.18 (m, 3H), 3.04 (m, 3H), 1.14 (d, 3H, J=6.16 Hz), 1.12 (s, 9H).

Workup

  1. customthe reaction was irradiated at 300 watts, 180° C. for 40 minutes or until HPLC
  2. customconsumption of starting material
  3. customthe product was isolated
  4. custompurified by Gilson prep HPLC

Sources & evidence

ORD record
ord-fdb0195f1def4bcc8efa74e1b3597aaa
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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