Diisopropylethylamine → HCID 178490212, compound

HRID 2279901Notes

Reaction equation

HRID 2279901 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[CH2:6][CH:7]=[CH:8][CH2:9][PH:10](=[O:14])[O:11][CH2:12][CH3:13].[CH3:21][C:22]1([CH3:38])[C:26]([CH3:28])([CH3:27])[O:25][B:24]([C:29]2[CH:30]=[N:31][N:32]([CH2:34]CCO)[CH:33]=2)[O:23]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[CH2:6][CH:7]=[CH:8][CH2:9][PH:10](=[O:14])[O:11][CH2:12][CH2:13][CH2:34][N:32]1[CH:33]=[C:29]([B:24]2[O:25][C:26]([CH3:28])([CH3:27])[C:22]([CH3:38])([CH3:21])[O:23]2)[CH:30]=[N:31]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 671871273-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol2×HCID 178476810HCID 178476810, compound2×

Product 1

HCID 178490212HCID 178490212, compoundYield 42.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A suspension of (3-methoxy-4-nitrobenzyl)prop-2-en-1-ylphosphinic acid (Compound 37E, 241 mg, 0.888 mmol) and 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 224 mg, 0.888 mmol) in 1,2-Dichloroethane (19 mL) and DIPEA (0.928 mL, 5.33 mmol) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (1387 mg, 2.665 mmol). The reaction mixture was stirred at rt for 16 hours. The reaction mixture was quenched with water (10 mL) and extracted with DCM (20 mL). The organic layer was washed with NaHCO3 (10 mL), washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a yellow oil. The crude material was purified on a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow oil. The material was re-purified on a Teledyne ISCO Combiflash® Rf system using 1:1 DCM-EtOAc/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow solid (189.6 mg, 42%). 1H NMR (CDCl3, 400 MHz): δ=7.81-7.87 (m, 2H), 7.71 (s, 1H), 7.11 (s, 1H), 6.92 (d, J=7.8 Hz, 1H), 5.73-5.86 (m, 1H), 5.19-5.32 (m, 2H), 4.27 (t, J=6.4 Hz, 2H), 3.90-4.04 (m, 5H), 3.20 (d, J=16.2 Hz, 2H), 2.61 (dd, J=7.6, 17.4 Hz, 2H), 2.15-2.25 (m, 2H), 1.33 (s, 12H). MS (ESI): m/z 506.63 [M+H]+. UPLC: tR=1.23 min (UPLC-SQD: analytical—2 min).

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with DCM (20 mL)
  3. washThe organic layer was washed with NaHCO3 (10 mL)
  4. washwashed with brine (15 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a yellow oil
  8. customThe crude material was purified on a Teledyne ISCO Combiflash® Rf system
  9. additionThe fractions containing product
  10. concentrationconcentrated under reduced pressure
  11. customto yield a light yellow oil
  12. customThe material was re-purified on a Teledyne ISCO Combiflash® Rf system
  13. additionThe fractions containing product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-05fb40852465406aab08ac53e16f0f4e
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

Loading…