Acetic Acid → HCID 178432466, compound

HRID 1695683Notes

Reaction equation

HRID 1695683 reaction equation
[C:1]([OH:4])(=O)[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.O[NH:18][C:19]([C:21]1[CH:40]=[CH:39][C:24]2[N:25]=[C:26]([NH:29][C@H:30]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][CH2:31]3)[O:27][CH2:28][C:23]=2[CH:22]=1)=[NH:20]>O1CCCC1>[C@H:30]1([NH:29][C:26]2[O:27][CH2:28][C:23]3[CH:22]=[C:21]([C:19]4[N:20]=[C:1]([CH3:2])[O:4][N:18]=4)[CH:40]=[CH:39][C:24]=3[N:25]=2)[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 178513220HCID 178513220, compound

Product 1

HCID 178432466HCID 178432466, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of acetic acid (67 mg, 1.12 mmol) in tetrahydrofuran (7.5 ml) was added at room temperature 1,1′-carbonyl-diimidazole (193 mg, 1.19 mmol). The mixture was allowed to stir for 15 min at room temperature and afterwards for 90 min at 70° C. N-hydroxy-2-((R)-indan-1-ylamino)-4H-benzo[d][1,3]oxazine-6-carboxamidine (Example 130) (240 mg, 0.74 mmol) was added at room temperature. The mixture was allowed to stir for 1 h at room temperature, evaporated to dryness and diluted with acetic acid (10 ml). The reaction mixture was allowed to stir for 2 h at 100° C., evaporated, poured into saturated sodium hydrogen carbonate solution (20 ml) and extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with brine (1×20 ml), dried (magnesium sulfate) and evaporated. The crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel and crystallization (dichloromethane/hexane) to yield the title compound as white solid (137 mg, 53%). MS (ISP): m/e=347.1 (M+H+); m.p. 138° C.

Workup

  1. stirringto stir for 1 h at room temperature
  2. customevaporated to dryness
  3. additiondiluted with acetic acid (10 ml)
  4. stirringto stir for 2 h at 100° C.
  5. customevaporated
  6. additionpoured into saturated sodium hydrogen carbonate solution (20 ml)
  7. extractionextracted with ethyl acetate (2×30 ml)
  8. washThe combined organic layers were washed with brine (1×20 ml)
  9. dry with materialdried (magnesium sulfate)
  10. customevaporated
  11. customThe crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel and crystallization (dichloromethane/hexane)

Sources & evidence

ORD record
ord-b464aa5b4d2649558c5702185158605a
Source dataset
uspto-grants-2012_04
Patent number
US08163740B2

Reaction notes

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