Hydrochloric Acid → 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-carboxamide

HRID 2272677Notes

Reaction equation

HRID 2272677 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[N:5]=[C:4]([C:19]2[S:23][C:22]([C:24]([CH:27]3[CH2:31][CH2:30][NH:29][CH2:28]3)([OH:26])[CH3:25])=[N:21][CH:20]=2)[CH:3]=1.[O-:32][C:33]#[N:34].[K+].O.Cl>O1CCCC1>[OH:26][C:24]([CH:27]1[CH2:31][CH2:30][N:29]([C:33]([NH2:34])=[O:32])[CH2:28]1)([C:22]1[S:23][C:19]([C:4]2[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([NH:8][C:9]3[CH:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:12]=[CH:11][N:10]=3)[N:5]=2)=[CH:20][N:21]=1)[CH3:25]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 11378442Potassium cyanateHCID 710036931-[5-(4-Methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol

Product 1

HCID 709844843-{1-Hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To the solution of 1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol (20 mg, 0.044 mmol, 1:1 mix of diastereomers) in tetrahydrofuran (0.4 mL) was added potassium cyanate (25 mg, 0.308 mmol), water (1.2 mL) and HCl (2 M in water, 0.14 mL, 0.280 mmol). The mixture was stirred at 55° C. for 3 hours then cooled to room temperature. The mixture was purified on reversed phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA) to afford 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-carboxamide as a 1:1 mixture of diastereomers. MS ESI calc'd. for C22H23F3N6O2S [M+H]+ 493. found 493. 1H NMR (500 MHz, CD3OD) δ 8.65-8.60 (m, 1H, two sets of doublets overlap from two diastereomers), 8.39 (d, 1H, two singlets from two diastereomers), 7.86 (s, 1H), 7.51 (d, 1H, two singlets from two diastereomers), 7.46-7.42 (m, 1H, two sets of doublets overlap from two diastereomers), 7.05 (s, 1H), 3.65-2.82 (m, 5H, two sets of peaks from two diastereomers), 2.50 (s, 3H), 2.20-2.00 (m, 2H), 1.69 (s, 3H). rhSyk activity=+++.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe mixture was purified on reversed phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-29a4e177a6474e30a4bb97130cc3ba9b
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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