Trifluoroacetic acid → Trifluoroacetic acid

HRID 1875918Notes

Reaction equation

HRID 1875918 reaction equation
C([O:8][C:9]1[N:14]=[C:13]2[S:15][C:16]([NH:18][C:19]3[O:20][C@:21]4([CH2:29][N:30]=3)[CH:26]3[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]3)[CH2:22]4)=[N:17][C:12]2=[CH:11][CH:10]=1)C1C=CC=CC=1.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]>>[N:23]12[CH2:24][CH2:25][CH:26]([CH2:27][CH2:28]1)[C@@:21]1([O:20][C:19]([NH:18][C:16]3[S:15][C:13]4[NH:14][C:9](=[O:8])[CH:10]=[CH:11][C:12]=4[N:17]=3)=[N:30][CH2:29]1)[CH2:22]2.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58088124(R)-N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

Product 2

HCID 6422Trifluoroacetic acidYield 39.8%HCID 58088071(R)-2-(4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octane]-2-ylamino)thiazolo[5,4-b]pyridin-5(4H)-one

Procedure

(R)—N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (390 mg, 0.925 mmol) was dissolved in TFA and allowed to react for 4 hours at ambient temperature, at which time LCMS and TLC showed the starting material to be mostly consumed. The TFA was removed in vacuo and the crude mixture was purified by preparative HPLC. The combined product fractions were concentrated in vacuo and triturated with ether to afford (R)-2-(4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]-2-ylamino)thiazolo[5,4-b]pyridin-5(4H)-one, TFA (164 mg, 0.368 mmol, 39.8% yield). M.P. 245 (dec). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.99 (br. s., 1H) 9.05 (br. s., 1H) 7.81 (d, J=8.53 Hz, 1H) 6.65 (d, J=8.78 Hz, 1H) 3.96 (d, J=10.29 Hz, 1H) 3.82 (d, J=10.54 Hz, 1H) 3.63-3.78 (m, 2H) 3.36-3.47 (m, 1H) 3.16-3.34 (m, 3H) 2.43 (br. s., 1H) 2.16 (br. s., 1H) 1.76-2.07 (m, 3H). MS (LC/MS) R.T.=0.50; [M+H]+=332.15.

Workup

  1. customto react for 4 hours at ambient temperature, at which time LCMS and TLC
  2. customto be mostly consumed
  3. customThe TFA was removed in vacuo
  4. customthe crude mixture was purified by preparative HPLC
  5. concentrationThe combined product fractions were concentrated in vacuo
  6. customtriturated with ether

Sources & evidence

ORD record
ord-2017022c776648769af7d5c21ad90b27
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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