Dimethylformamide → HCID 71457481, compound

HRID 631931Notes

Reaction equation

HRID 631931 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[N:15]([CH3:26])[N:16]=[N:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3([C:47]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])=[O:48])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)O1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].Cl[Pd]Cl>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[N:15]([CH3:26])[N:16]=[N:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22]([C:38]3[CH:39]=[CH:40][C:41]([C:44]4([C:47]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])=[O:48])[CH2:46][CH2:45]4)=[CH:42][CH:43]=3)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 66577823N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamideHCID 131735432[5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester

Product 1

HCID 71457481HCID 71457481, compoundYield 41.8%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 20 mL vial, [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester (123.7 mg, 264 μmol), N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide (110 mg, 301 μmol), DPPF (36 mg, 64.9 μmol) and PdCl2(dppOCH2Cl2 (40 mg, 49.0 μmol) were combined with DMF (5 mL, with nitrogen bubbled through for 20 min) to give a light brown/red solution. To this was added 2N Na2CO3 (527 μl, 1.05 mmol, with nitrogen bubbled through for 20 min), the red mixture (looked like salt precipitated) had nitrogen bubbled through for 1 min. The vial was sealed, placed in a dry block, and heated at 80° C. for 4 hr. The reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (75 mL). The organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and dried from DCM/hexanes to give a crude material (311 mg). The crude material was dissolved in minimal DCM and purified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH). Appropriate fractions were combined, concentrated, dried from DCM/hexanes to yield {5-[4′-(1-methane-sulfonylamino carbonyl-cyclopropyl)-biphenyl-4-yl]-3-methyl-3H-[1,2,3]triazol-4-yl}-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester (69.2 mg, 41.8% yield) as a brown solid. C30H28F3N5O5S (m/e) 627, obsd. 628 (M+H, ES+). 1H NMR (DMSO-d6) δ ppm 11.16 (br. s., 1H), 9.47-10.15 (m, 1H), 7.53-7.94 (m, 10H), 7.41 (d, J=8.3 Hz, 2H), 5.89 (br. s., 1H), 3.86 (br. s., 3H), 3.20 (s, 3H), 1.60 (br. s., 3H), 1.47-1.53 (m, 2H), 1.20 (d, J=1.8 Hz, 2H).

Workup

  1. customto give a light brown/red solution
  2. customthe red mixture (looked like salt precipitated)
  3. custombubbled through for 1 min
  4. customThe vial was sealed
  5. additionThe reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL)
  6. customThe layers were separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (75 mL)
  8. washThe organic layers were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dry with materialdried from DCM/hexanes
  13. customto give a crude material (311 mg)
  14. custompurified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH)
  15. concentrationconcentrated
  16. dry with materialdried from DCM/hexanes

Sources & evidence

ORD record
ord-ab13aa95989a478eb96c30cecb88c3ca
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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