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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 2272676
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HRID 2272676 반응식
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
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반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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=+++.

후처리

  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)

출처 및 근거

ORD 기록
ord-321cf60f3c61402d96048200b6ea7924
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09120785B2

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