1H-Indazole → HCID 25165085, compound

HRID 1752550Notes

Reaction equation

HRID 1752550 reaction equation
[C:1]1([CH2:7][C:8]#[CH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:10]=[N+:11]=[N-:12].[Na+].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].C(=O)([O-])[O-].[Na+].[Na+].N1CCC[C@H]1C(O)=O.[OH-].[Na+].[NH:43]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=[N:44]1>C(OCC)(=O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O.CS(C)=O>[CH2:7]([C:8]1[N:10]=[N:11][N:12]([C:48]2[CH:47]=[C:46]3[C:51](=[CH:50][CH:49]=2)[NH:43][N:44]=[CH:45]3)[CH:9]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

12

Reactant 7

HCID 92211H-IndazoleHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 145742L-ProlineHCID 575753BenzylacetyleneHCID 23667548Sodium Ascorbate

Product 1

HCID 25165085HCID 25165085, compound

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Example 87A (969 mg, 3.39 mmol), 3-phenyl-1-propyne (392 mg, 3.37 mmol), sodium azide (278 mg, 4.28 mmol), sodium ascorbate (68 mg, 3.43 mmol), sodium carbonate (75 mg, 0.708 mmol), and L-proline (78 mg, 8.98 mmol) were combined in a 1:1 mixture of dimethyl sulfoxide and water (10 mL). Copper(II) sulfate pentahydrate (46 mg, 0.184 mmol) was added and the mixture was stirred at 65° C. for 3 hours. 6 N Sodium hydroxide (1 mL) was added, and the mixture was stirred for 30 minutes to deprotect the indazole. The mixture was diluted with ethyl acetate and washed with 1 N hydrochloric acid. The organic layer was concentrated under reduced pressure, and the resulting residue was triturated with methanol. The remaining solids were absorbed on silica gel and purified by silica gel chromatography eluting with a gradient of 0-5% methanol in dichloromethane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 13.35 (s, 1H) 8.58 (s, 1H) 8.17-8.27 (m, 1H) 7.86 (d, J=8.82, 2.03 Hz, 1H) 7.67-7.77 (m, 1H) 7.27-7.36 (m, 2H) 7.18-7.27 (m, 1H) 4.10 (s, 1H). MS (ESI+) m/z 276.0 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. washwashed with 1 N hydrochloric acid
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. customthe resulting residue was triturated with methanol
  5. customThe remaining solids were absorbed on silica gel
  6. custompurified by silica gel chromatography
  7. washeluting with a gradient of 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-b9fc1d204f32463eb13aaf1ecfed526f
Source dataset
uspto-grants-2015_10
Patent number
US09163007B2

Reaction notes

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