Indoline → HCID 76281598, compound

HRID 929812Notes

Reaction equation

HRID 929812 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH:24]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:36]=[C:35]([C:37]([NH2:39])=[O:38])[O:34][N:33]=2)=[CH:28][CH:27]=1)=O.C([O-])([O-])=O.[Na+].[Na+]>ClC(Cl)C.CC(O)=O>[N:1]1([CH2:24][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH:36]=[C:35]([C:37]([NH2:39])=[O:38])[O:34][N:33]=3)=[CH:30][CH:31]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 10328IndolineHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 90202333HCID 90202333, compound2×

Product 1

HCID 76281598HCID 76281598, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of indoline (13 μL, 0.116 mmol) in dichloroethane (1 mL) was added Na(OAc)3BH (74 mg, 0.35 mmol). The mixture was stirred at room temperature under argon for 20 min. A slurry of 3-(4-formyl-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 20; 25 mg, 0.116 mmol) in dichloroethane (1 mL) was added, followed by AcOH (20 μL). The reaction mixture was stirred at room temperature overnight. 1 M Na2CO3 solution was added and the mixture was extracted with EtOAc (3×25 mL). The organic layer was washed with brine, dried (Na2SO4), evaporated, and purified by chromatography (12.5-20% acetone/CH2Cl2) to give 3-[4-(2,3-dihydro-indol-1-ylmethyl)-phenyl]-isoxazole-5-carboxylic acid amide (24 mg, 65%), as an off-white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.27 (br. s., 1H), 7.90 (br. s., 1H), 7.79 (d, J=8.2 Hz, 2H), 7.48 (s, 1H), 7.41 (d, J=8.2 Hz, 2H), 6.95 (d, J=6.9 Hz, 1H), 6.88 (t, J=7.7 Hz, 1H), 6.42-6.55 (m, 2H), 4.23 (s, 2H), 3.14-3.21 (m, 2H), 2.75-2.87 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with EtOAc (3×25 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. custompurified by chromatography (12.5-20% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-d5c21b03df514f9089d53887ee609460
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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