Dimethylformamide → HCID 71452129, compound

HRID 631929Notes

Reaction equation

HRID 631929 reaction equation
[C:1]1([C@H:7]([O:9][C:10](=[O:25])[NH:11][C:12]2[N:13]([CH3:24])[N:14]=[N:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([C:40]3([C:43]([NH:45][S:46]([CH3:49])(=[O:48])=[O:47])=[O:44])[CH2:42][CH2:41]3)=[CH:36][CH:35]=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]>[C:1]1([C@H:7]([O:9][C:10](=[O:25])[NH:11][C:12]2[N:13]([CH3:24])[N:14]=[N:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([C:34]3[CH:35]=[CH:36][C:37]([C:40]4([C:43]([NH:45][S:46]([CH3:49])(=[O:48])=[O:47])=[O:44])[CH2:42][CH2:41]4)=[CH:38][CH:39]=3)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 66577823N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamideHCID 71266457HCID 71266457, compound

Product 1

HCID 71452129HCID 71452129, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 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-phenyl-ethyl ester (Example 1, 110.3 mg, 275 μmol), N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide (112 mg, 307 μmol), DPPF (38 mg, 68.5 μmol) and PdCl2(dppf)CH2Cl2 (39 mg, 47.8 μmol) were combined with DMF (5 mL) and the mixture was bubbled with nitrogen for 20 minutes to give a light brown/red solution. To this was added 2N Na2CO3 (550 μL, 1.1 mmol, degassed with nitrogen bubbled through for 20 min), and 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), and 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 and DCM to yield {5-[4′-(1-methanesulfonylaminocarbonyl-cyclopropyl)-biphenyl-4-yl]-3-methyl-3H-[1,2,3]triazol-4-yl}-carbamic acid (R)-1-phenyl-ethyl ester (98.5 mg, 64% yield). LC/MS calcd. for C29H29N5O5S (m/e) 559, obsd. 560 (M+H, ES+). 1H NMR (DMSO-d6) δ ppm 11.16 (br. s., 1H), 9.93 (br. s., 1H), 7.80 (d, J=7.8 Hz, 2H), 7.62-7.76 (m, 4H), 7.06-7.57 (m, 7H), 5.65-5.93 (m, 1H), 3.85 (s, 3H), 3.20 (s, 3H), 1.38-1.76 (m, 5H), 1.20 (br. s., 2H).

Workup

  1. customthe mixture was bubbled with nitrogen for 20 minutes
  2. customto give a light brown/red solution
  3. customthe red mixture (looked like salt precipitated)
  4. custombubbled through for 1 min
  5. customThe vial was sealed
  6. additionThe reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL)
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with ethyl acetate (75 mL)
  9. washThe organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dry with materialdried from DCM/hexanes
  14. customto give a crude material (311 mg)
  15. custompurified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH)
  16. concentrationconcentrated
  17. dry with materialdried from DCM/hexanes and DCM

Sources & evidence

ORD record
ord-a3da9e5e20cb420d86df829626c6cd8e
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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