Trifluoroacetic acid → HCID 16058857, compound

HRID 1172370Notes

Reaction equation

HRID 1172370 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][C@@H:12]([NH:43][C:44]([N:46]2[CH2:51][CH2:50][CH:49]([C:52]3[C:53](=[O:62])[NH:54][C:55]4[C:60]([CH:61]=3)=[CH:59][CH:58]=[CH:57][CH:56]=4)[CH2:48][CH2:47]2)=[O:45])[C:13]([NH:15][C@H:16]([C:29](=[O:42])[N:30]2[CH2:35][CH2:34][N:33]([C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)[CH2:32][CH2:31]2)[CH2:17][CH2:18][CH2:19][CH2:20][NH:21]C(=O)OC(C)(C)C)=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.FC(F)(F)C(O)=O>ClCCl>[NH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C@H:16]([NH:15][C:13](=[O:14])[C@H:12]([NH:43][C:44]([N:46]1[CH2:51][CH2:50][CH:49]([C:52]2[C:53](=[O:62])[NH:54][C:55]3[C:60]([CH:61]=2)=[CH:59][CH:58]=[CH:57][CH:56]=3)[CH2:48][CH2:47]1)=[O:45])[CH2:11][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([CH3:1])[CH:3]=1)[NH:9][N:8]=[CH:7]2)[C:29](=[O:42])[N:30]1[CH2:31][CH2:32][N:33]([C:36]2[CH:37]=[CH:38][N:39]=[CH:40][CH:41]=2)[CH2:34][CH2:35]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 15953808HCID 15953808, compound

Product 1

HCID 16058857HCID 16058857, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of tert-butyl (S)-5-((R)-3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamido)propanamido)-6-oxo-6-(4-(pyridin-4-yl)piperazin-1-yl)hexylcarbamate (230 mg, 0.27 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (10 mL) at 0° C. After 1 h at room temperature, the solvent was removed under high vacuum and then dissolved in methanol. The free base of title compound was liberated by passing the methanolic solution over Strata-X—C-33μ cation polymeric sorbent followed by elution with 3.0 M ammonia solution in methanol to give N-((R)-1-((S)-6-amino-1-oxo-1-(4-(pyridin-4-yl)piperazin-1-yl)hexan-2-ylamino)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide as a white solid in 72% yield. 1H-NMR (CD3OD) δ 8.08-8.07 (m, J=2, 2H), 7.95 (s, 1H), 7.61 (d, J=10 Hz, 1H), 7.51-7.44 (m, 3H), 7.29 (d, J=10 Hz, 1H), 7.23-7.19 (m, 1H), 7.11 (s, 1H), 6.79-6.78 (m, 2H), 4.80-4.77 (m, 2H), 4.60-4.55 (m, 1H), 4.11-4.04 (m, 2H), 3.82-3.80 (m, 2H), 3.66-2.78 (m, 11H), 2.51 (s, 3H), 1.87-1.11 (m, 11H; MS (ESI) 747 (M+H); Rf=1.64.

Workup

  1. customthe solvent was removed under high vacuum
  2. dissolutiondissolved in methanol
  3. washfollowed by elution with 3.0 M ammonia solution in methanol

Sources & evidence

ORD record
ord-e5485011f4e7450f8168900dc68f7128
Source dataset
uspto-grants-2010_11
Patent number
US07834007B2

Reaction notes

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