Hydrochloric Acid → N-tert-Butyl-3-[2-(2-methoxy-4-piperidin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-benzenesulfonamide

HRID 1262112Notes

Reaction equation

HRID 1262112 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:26]=[CH:25][C:24]4=[CH:27][CH:28]=[C:29]([C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([S:36](=[O:43])(=[O:42])[NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:31]=5)[N:23]4[N:22]=3)=[C:16]([O:44][CH3:45])[CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)(=O)C>C(Cl)Cl>[C:38]([NH:37][S:36]([C:32]1[CH:33]=[CH:34][CH:35]=[C:30]([C:29]2[N:23]3[C:24]([CH:25]=[N:26][C:21]([NH:20][C:17]4[CH:18]=[CH:19][C:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)=[CH:15][C:16]=4[O:44][CH3:45])=[N:22]3)=[CH:27][CH:28]=2)[CH:31]=1)(=[O:43])=[O:42])([CH3:41])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 667120084-{4-[7-(3-tert-Butylsulfamoyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66711286N-tert-Butyl-3-[2-(2-methoxy-4-piperidin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-benzenesulfonamideYield 39.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-{4-[7-(3-tert-Butylsulfamoyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidine-1-carboxylic acid tert-butyl ester (207.0 mg, 0.31 mmol) in 6.0 mL of DCM at room temperature was added hydrogen chloride gas. When deprotection was complete, ethyl acetate was added, and the precipitate was filtered and washed with ethyl acetate. The orange solid was taken up in water, treated with sat. NaHCO3 until aq. layer pH=13, and extracted with DCM. The organic layers were combined, dried with sodium sulfate, filtered, and conc. in vacuo to afford N-tert-Butyl-3-[2-(2-methoxy-4-piperidin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-benzenesulfonamide as a burnt orange solid (65 mg, 39%). MP 201-202° C. LCMS (E/I+) 535.21 (M+H). 1H NMR (DMSO-d6)-9.01 (s, 1H), 8.56 (s, 1H), 8.36 (d, 1H, J=7.76 Hz), 7.99 (d, 1H, J=8.56 Hz), 7.85 (s, 1H), 7.83 (s, 1H), 7.69 (t, 1H, J=7.84 Hz), 7.23 (d, 1H, J=4.76 Hz), 7.01 (d, 1H, J=4.72 Hz), 6.95-6.89 (m, 2H), 3.32 (s, 3H), 3.10-2.98 (m, 2H), 2.69-2.52 (m, 2H), 1.78-1.69 (m, 2H), 1.69-1.44 (m, 2H), 1.12 (s, 9H).

Workup

  1. filtrationthe precipitate was filtered
  2. washwashed with ethyl acetate
  3. additiontreated with sat. NaHCO3 until aq. layer pH=13
  4. extractionextracted with DCM
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered

Sources & evidence

ORD record
ord-f4251c2a89a74125958f3a2eb011d5f5
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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