Potassium Carbonate → (R)-tert-butyl 4-(2-(3-cyano-4-isopropoxyphenyl)oxazol-5-yl)-2,3-dihydro-1H-inden-1-ylcarbamate

HRID 1053758Notes

Reaction equation

HRID 1053758 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][CH2:12][C@H:13]3[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])O1.Br[C:28]1[O:32][C:31]([C:33]2[CH:34]=[CH:35][C:36]([O:41][CH:42]([CH3:44])[CH3:43])=[C:37]([CH:40]=2)[C:38]#[N:39])=[N:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CC(O)C(O)C.O>>[C:38]([C:37]1[CH:40]=[C:33]([C:31]2[O:32][C:28]([C:9]3[CH:17]=[CH:16][CH:15]=[C:14]4[C:10]=3[CH2:11][CH2:12][C@H:13]4[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[CH:29][N:30]=2)[CH:34]=[CH:35][C:36]=1[O:41][CH:42]([CH3:44])[CH3:43])#[N:39]

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 583549795-(5-Bromooxazol-2-yl)-2-isopropoxybenzonitrileHCID 58355082(R)-tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-ylcarbamateHCID 122674143dimethylethylene glycol H2O

Product 1

HCID 58355072(R)-tert-butyl 4-(2-(3-cyano-4-isopropoxyphenyl)oxazol-5-yl)-2,3-dihydro-1H-inden-1-ylcarbamateYield 67%

Procedure

Prepared using General Procedure 13. A 20 mL microwave vial was charged with (R)-tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-32 (58.4 mg, 0.16 mmol), 5-(5-bromooxazol-2-yl)-2-isopropoxybenzonitrile INT-40 (50 mg, 0.16 mmol), potassium carbonate (68 mg, 0.5 mmol) and a 3:1 mixture of dimethylethylene glycol/H2O (2 mL). The reaction mixture was degassed by bubbling N2 gas through the stirring solution for 10 min. Pd(PPh3)4 ((3.9 mg, 0.004 mmol) was added and the solution degassed for additional 2 min. The vial was subjected to microwave irradiation at 100° C. for 30 min. The solvent was removed and the residue dissolved in EA (10 mL), washed with brine, and then dried over MgSO4. The product was purified by chromatography (EA/hexanes) to afford 50 mg (67%) of (R)-tert-butyl 4-(2-(3-cyano-4-isopropoxyphenyl)oxazol-5-yl)-2,3-dihydro-1H-inden-1-ylcarbamate INT-42 as an off-white solid. LCMS-ESI (m/z) calculated for C27H29N3O4: 459.5; found 460.2 [M+H]+, tR=4.1 min. 1H NMR (400 MHz, CDCl3) δ 8.32-8.03 (m, 2H), 7.60 (dd, J=8.6, 4.1 Hz, 1H), 7.32-7.22 (m, 3H), 7.00 (d, J=8.9 Hz, 1H), 5.19 (dd, J=15.5, 7.5 Hz, 1H), 4.82-4.56 (m, 2H), 3.12 (ddd, J=16.3, 9.0, 3.5 Hz, 1H), 2.95 (dt, J=16.3, 8.1 Hz, 1H), 2.70-2.51 (m, 1H), 1.83 (dq, J=13.1, 8.2 Hz, 1H), 1.43 (s, 9H), 1.41-1.35 (m, 6H).

Workup

  1. customPrepared
  2. customThe reaction mixture was degassed
  3. customby bubbling N2 gas through the stirring solution for 10 min
  4. additionPd(PPh3)4 ((3.9 mg, 0.004 mmol) was added
  5. customthe solution degassed for additional 2 min
  6. customirradiation at 100° C. for 30 min
  7. customThe solvent was removed
  8. dissolutionthe residue dissolved in EA (10 mL)
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. customThe product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-e0dcb79c2c0f415288db356ff8e83eed
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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