Triethylamine → HCID 68172892, compound

HRID 1408871Notes

Reaction equation

HRID 1408871 reaction equation
C(OC(=O)[NH:7][C@@:8]12[CH2:15][C@@:12]([NH:16][C:17]([C:19]3[CH:24]=[N:23][CH:22]=[C:21]([CH3:25])[N:20]=3)=[O:18])([CH2:13][CH2:14]1)[CH2:11][CH2:10][CH2:9]2)(C)(C)C.[CH3:27][C:28]1[N:29]=[C:30]([C:33]([OH:35])=O)[S:31][CH:32]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.Cl.O1CCOCC1>[CH3:27][C:28]1[N:29]=[C:30]([C:33]([NH:7][C@@:8]23[CH2:15][C@@:12]([NH:16][C:17]([C:19]4[CH:24]=[N:23][CH:22]=[C:21]([CH3:25])[N:20]=4)=[O:18])([CH2:13][CH2:14]2)[CH2:11][CH2:10][CH2:9]3)=[O:35])[S:31][CH:32]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 224993364-Methyl-1,3-thiazole-2-carboxylic acidHCID 70497815HCID 70497815, compound2×

Product 1

HCID 68172892HCID 68172892, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of {(1R,5S)-5-[(6-methyl-pyrazine-2-carbonyl)-amino]-bicyclo[3.2.1]oct-1-yl}-carbamic acid tert-butyl ester (intermediate 13, 0.050 g, 0.14 mmol) in 1 mL of methylene chloride, 4 M of hydrogen chloride in 1,4-dioxane (0.5 mL) was added. After stirring at rt overnight, the reaction mixture was concentrated under reduced pressure to dryness. The resulting residue was dissolved in methylene chloride (1.0 mL), 4-methyl-1,3-thiazole-2-carboxylic acid (19.8 mg, 0.14 mmol), triethylamine (7.73 μL, 0.56 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (61.4 mg, 0.14 mmol) were added. After stirring at rt for 1 hour, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified on the CombiFlash® system (hexane/ethyl acetate: 100/0 to 10/90 in 10 mins, then hexane/ethyl acetate: 10/90) to afford 31 mg (58%) of 6-methyl-pyrazine-2-carboxylic acid {(1S,5R)-5-[(4-methyl-thiazole-2-carbonyl)-amino]-bicyclo[3.2.1]oct-1-yl}-amide. Analytical data are listed in Table 3.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure to dryness
  2. dissolutionThe resulting residue was dissolved in methylene chloride (1.0 mL)
  3. stirringAfter stirring at rt for 1 hour
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customThe resulting residue was purified on the CombiFlash® system (hexane/ethyl acetate
  6. wait100/0 to 10/90 in 10 mins

Sources & evidence

ORD record
ord-13f25db823624dc9b2a38d05cbc3c571
Source dataset
uspto-grants-2014_12
Patent number
US08921370B2

Reaction notes

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