Trifluoroacetic acid → 1-[5-(4-Methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol

HRID 2272676Notes

Reaction equation

HRID 2272676 reaction equation
FC(F)(F)C(O)=O.[OH:8][C:9]([CH:34]1[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35]1)([C:11]1[S:12][C:13]([C:16]2[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([NH:23][C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=3)[N:17]=2)=[CH:14][N:15]=1)[CH3:10]>ClCCl>[CH3:22][C:20]1[CH:19]=[C:18]([NH:23][C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:27]=[CH:26][N:25]=2)[N:17]=[C:16]([C:13]2[S:12][C:11]([C:9]([CH:34]3[CH2:38][CH2:37][NH:36][CH2:35]3)([OH:8])[CH3:10])=[N:15][CH:14]=2)[CH:21]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86715346Tert-butyl 3-{1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)-pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxylate

Product 1

HCID 710036931-[5-(4-Methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.4 mL, 5.19 mmol) was added to a solution of tert-butyl 3-{1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxylate (100 mg, 0.182 mmol) in dichloromethane (0.8 mL). The mixture was stirred at room temperature for 16 hours then concentrated under reduced pressure. The residue was purified on reverse phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA) to afford 1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol as a 1:1 mix of diastereomers. MS ESI calc'd. for C21H22F3N5OS [M+H]+ 450. found 450. 1H NMR (500 MHz, CD3OD) δ 8.55 (d, J=5.6 Hz, 1H), 8.37 (d, 11-1, two singlets from two diastereomers), 8.12 (s, 1H), 7.46 (s, 1H), 7.37 (d, J=5.5 Hz, 1H), 7.05 (s, 1H), 3.58-2.95 (m, 5H, two sets of peaks from two diastereomers), 2.45 (s, 3H), 2.30-1.79 (m, 2H, two sets of peaks from two diastereomers), 1.69 (d, 3H, two singlets from two diastereomers). rhSyk activity=+++.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue was purified on reverse phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-321cf60f3c61402d96048200b6ea7924
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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