Methoxyacetic Acid → HCID 59275601, compound

HRID 555098Notes

Reaction equation

HRID 555098 reaction equation
[CH3:1][O:2][CH2:3][C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:19][C:20]1[C:39]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([C:46](=[O:57])[NH:47][C:48]3([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[CH2:50][CH2:49]3)[CH:41]=2)=[CH:38][C:23]2[C:24]([C:34]([NH:36][CH3:37])=[O:35])=[C:25]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[O:26][C:22]=2[CH:21]=1.N12CCCN=C1CCCCC2>C1COCC1.CO>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([NH:19][C:4](=[O:6])[CH2:3][O:2][CH3:1])[C:39]([C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([C:46](=[O:57])[NH:47][C:48]5([C:51]6[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=6)[CH2:50][CH2:49]5)[CH:41]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 12251Methoxyacetic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59275318HCID 59275318, compound

Product 1

HCID 59275601HCID 59275601, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of 2-methoxyacetic acid (10.40 mg, 0.115 mmol) in THF (3 mL) at r.t. under N2 was added 1,1′-carbonyldiimidazole (CDI) (28.1 mg, 0.173 mmol). The mixture was stirred at 55° C. for 1 hr. The mixture was then transferred to a flask containing 6-amino-2-(4-fluorophenyl)-N-methyl-5-(3-(1-phenylcyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide (30 mg, 0.058 mmol) at r.t. under N2. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (0.035 mL, 0.231 mmol) was then added and the mixture was stirred at 55° C. for 2 hr 35 min. The mixture was then left standing at r.t. overnight. The mixture was re-stirred at 55° C. for 3 hr. The mixture was cooled to r.t., diluted with MeOH and purified by Shimadzu-VP preparative reverse phase HPLC using the separation method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=50, Final % B=100, Gradient time=10 min, Stop time=12 min, Flow Rate=25 mL/min, Column: Waters-Sunfire 19×100 mm S5, Fraction Collection: 7.28-7.84 min. (UV detection at 220 nm). 1H NMR (500 MHz, DMSO-d6) δ 9.29 (s, 1H), 9.04 (s, 1H), 8.49 (q, J=4.58, 1H), 8.31 (s, 1H), 8.03-8.00 (overlapping m, 3H), 7.98 (m, 1H), 7.59 (s, 1H), 7.63 (s, 1H), 7.625 (d, J=2.44, 1H), 7.40 (t, J=9.00, 2H), 7.28 (apparent t, J=7.63, 2H,), 7.23 (apparent d, 2H,), 7.17 (t, J=7.17, 1H,), 3.90 (s, 2H), 3.18 (s, 3H), 2.83 (appeared as d, J=4.58, 3H), 1.28 (s, 4H). LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=4 ml/min, Column: XTERRA® MS 7 um, C18, 3.0×50 mm; (ES+) m/z (M+H)+=592.49, HPLC Rt=1.652 min.

Workup

  1. customThe mixture was then transferred to a flask
  2. stirringthe mixture was stirred at 55° C. for 2 hr 35 min
  3. waitThe mixture was then left
  4. waitstanding at r.t. overnight
  5. stirringThe mixture was re-stirred at 55° C. for 3 hr
  6. temperatureThe mixture was cooled to r.t.
  7. custompurified by Shimadzu-VP preparative reverse phase HPLC
  8. customthe separation method
  9. customB=100, Gradient time=10 min
  10. customtime=12 min, Flow Rate=25 mL/min, Column
  11. customWaters-Sunfire 19×100 mm S5, Fraction Collection
  12. custom7.28-7.84 min. (UV detection at 220 nm)
  13. customB=100, Gradient time=2 min
  14. customtime=3 min, Flow Rate=4 ml/min, Column

Sources & evidence

ORD record
ord-b5fc2fb694a046faa93cb4fe112d6313
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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