Ammonium Hydroxide → HCID 58020127, compound

HRID 1632071Notes

Reaction equation

HRID 1632071 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:26][CH2:25][C@@H:24]4[C:27](O)=[O:28])=[N:21][CH:22]=3)[C:9]=2[F:30])[CH:5]=[CH:6][CH:7]=1.C([N:34](CC)C(C)C)(C)C.C(OC(Cl)=O)C(C)C.[OH-].[NH4+]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:26][CH2:25][C@@H:24]4[C:27]([NH2:34])=[O:28])=[N:21][CH:22]=3)[C:9]=2[F:30])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 81531DiisopropylethylamineHCID 42610875HCID 42610875, compound

Product 1

HCID 58020127HCID 58020127, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cooled 0-5° C. and stirred solution of (R)-1-[5-(3′-chloro-2-fluoro-6methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-azetidine-2-carboxylic acid (I-144, 0.14 g, 0.33 mmol) in THF (2.5 mL) was added N,N-diisopropylethylamine (0.09 g, 0.69 mmol). The reaction mixture was stirred for 5 min, isobutylchloroformate (0.05 g, 0.36 mmol) was added, and the reaction stirred at 0-5° C. for 30 min. Ammonium hydroxide solution (28%, 1.0 mL, 8.0 mmol) was added, the reaction warmed to room temperature, and stirred for 0.5 h. The reaction mixture was diluted with water (5 mL). The organic layer was separated, the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using 5% methanol in dichloromethane, followed by preparative thin layer chromatography using 5% methanol in dichloromethane to afford 0.07 g (47%) of P-617 as an off-white solid. 1H NMR (DMSO-d6, 400 MHz): 7.99 (d, J=2.8 Hz, 1H), 7.51 (br s, 1H), 7.38-7.46 (m, 3H), 7.4 (br s, 1H), 7.24-7.3 (m, 2H), 7.14 (br s, 1H), 6.92 (d, J=8.4 Hz, 1H), 6.34 (d, J=8.0 Hz, 1H), 4.39 (dd, J=9.6, 6.8 Hz, 1H), 3.7-3.9 (m, 2H), 3.84 (s, 2H), 3.72 (s, 3H), 2.26-2.48 (m, 2H) ppm; MS (APCI+): 426.9 (M+1), LC-MS: 100%.

Workup

  1. stirringthe reaction stirred at 0-5° C. for 30 min
  2. stirringstirred for 0.5 h
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  5. dry with materialThe combined organic layers were dried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography
  9. customto afford 0.07 g (47%) of P-617 as an off-white solid

Sources & evidence

ORD record
ord-31757fd679e14c1fa2b9e2e046fc9bdf
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

Loading…