Trifluoroacetic acid → Trifluoroacetic acid

HRID 1262120Notes

Reaction equation

HRID 1262120 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11](O)([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]=[CH:32][C:31]=5[N:36]([S:38]([CH3:41])(=[O:40])=[O:39])[CH3:37])[N:23]4[N:22]=3)=[C:16]([O:42][CH3:43])[CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]>ClCCl>[CH3:43][O:42][C:16]1[CH:15]=[C:14]([C:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=2)[CH:19]=[CH:18][C:17]=1[NH:20][C:21]1[N:26]=[CH:25][C:24]2=[CH:27][CH:28]=[C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[N:36]([CH3:37])[S:38]([CH3:41])(=[O:40])=[O:39])[N:23]2[N:22]=1.[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 667114924-Hydroxy-4-(4-{7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 6422Trifluoroacetic acidHCID 66711801HCID 66711801, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Hydroxy-4-(4-{7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (41 mg) was dissolved in dichloromethane (1 ml), and trifluoroacetic acid (1 ml) was added. The solution was stirred 2 hours at room temperature, and then concentrated. Purification on Gilson reverse phase chromatograph (15% to 45% acetonitrile/water gradient) and lyophilization afforded N-(2-{2-[2-methoxy-4-(1,2,3,6-tetrahydro-pyridin-4-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-N-methyl-methanesulfonamide, compound with trifluoroacetic acid as an orange solid, 16 mg. mp 204-205° C. LCMS (E/I+) 505 (M+H). NMR 1H (DMSO-d6) 9.01 (s, 1H), 8.85 (br s, 1H), 7.98-8.05 (m, 2H), 7.80 (s, 1H), 7.64-7.70 (m, 1H), 7.51-7.62 (m, 2H), 7.24-7.48 (m, 1H), 7.11 (s, 1H), 6.98-7.05 (m, 2H), 6.91-6.96 (d, J=4.56, 1H), 6.21 (s, 1H), 3.88 (s, 3H), 3.65-3.82 (m, 2H), 3.39-3.48 (m, 2H), 3.12 (s, 3H), 2.87 (s, 3H), 2.55-2.64 (m, 2H), 2.32 (s, 1H).

Workup

  1. concentrationconcentrated
  2. customPurification on Gilson reverse phase chromatograph (15% to 45% acetonitrile/water gradient) and lyophilization

Sources & evidence

ORD record
ord-b353db37aa004a10804e8c4994a36386
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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