Methanol → HCID 68992268, compound

HRID 657056Notes

Reaction equation

HRID 657056 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[N:10]([CH2:11][CH:12]=O)[C:9](=[O:14])[S:8][C:5]2=[N:6][CH:7]=1.[O:15]1[C:24]2[CH:23]=[C:22]([CH2:25][N:26]([CH:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)C(=O)OC(C)(C)C)[N:21]=[CH:20][C:19]=2[O:18][CH2:17][CH2:16]1.CO.FC(F)(F)C(O)=O.C(Cl)(Cl)[Cl:50]>C(O)(=O)C.C(Cl)Cl>[ClH:50].[ClH:50].[O:15]1[C:24]2[CH:23]=[C:22]([CH2:25][NH:26][CH:34]3[CH2:39][CH2:38][N:37]([CH2:12][CH2:11][N:10]4[C:4]5[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=5)[S:8][C:9]4=[O:14])[CH2:36][CH2:35]3)[N:21]=[CH:20][C:19]=2[O:18][CH2:17][CH2:16]1

Participants

8

Reactant 5

HCID 887MethanolHCID 6212ChloroformHCID 6422Trifluoroacetic acidHCID 578154611,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamateHCID 86635344HCID 86635344, compound

Product 1

HCID 68992268HCID 68992268, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

(6-fluoro-2-oxo[1,3]thiazolo[5,4-b]pyridin-1(2H)-yl)acetaldehyde (0.046 g, 0.22 mmole) and 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate (0.069 g, 0.2 mmole) (for a synthesis see WO2004/058144 Example 99(h)) were dissolved in chloroform (5 ml) and MeOH (1 ml) and treated with acetic acid (10 drops) and (polystyrylmethyl)trimethylammonium cyanoborohydride (Novabiochem) (4.1 mmol/g, 0.39 g), and the mixture stirred at rt for 60 h. The reaction was filtered and evaporated to dryness to give 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl) {1-[2-(6-fluoro-2-oxo[1,3]thiazolo[5,4-b]pyridin-1(2H)-yl)ethyl]-4-piperidinyl}. This was dissolved in DCM (3 ml) and treated with trifluoroacetic acid (1 ml) at rt for 4 h then evaporated to dryness. The residue was dissolved in MeOH, stirred with polymer supported carbonate resin and then filtered and evaporated. Chromatography on silica gel of the residue, eluting with a gradient of 0-12% 2M ammonia in MeOH/DCM gave the free base of the title compound (0.05 g, 51%)

Workup

  1. filtrationThe reaction was filtered
  2. customevaporated to dryness
  3. customto give 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl) {1-[2-(6-fluoro-2-oxo[1,3]thiazolo[5,4-b]pyridin-1(2H)-yl)ethyl]-4-piperidinyl}
  4. customthen evaporated to dryness
  5. dissolutionThe residue was dissolved in MeOH
  6. stirringstirred with polymer
  7. filtrationfiltered
  8. customevaporated
  9. washChromatography on silica gel of the residue, eluting with a gradient of 0-12% 2M ammonia in MeOH/DCM

Sources & evidence

ORD record
ord-32a6bafb5d98478b8ff8a145a972d4c3
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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