Lithium Hydroxide → HCID 46853082, compound

HRID 2199702Notes

Reaction equation

HRID 2199702 reaction equation
[Li+].[OH-].Br[C:4]1[C:12]2[S:11][CH:10]=[C:9]([CH:13]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)[C@@H:14]([C:19]3[CH:34]=[CH:33][C:22]([C:23]([NH:25][CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])=[O:24])=[CH:21][CH:20]=3)[CH2:15][CH2:16][CH2:17][CH3:18])[C:8]=2[CH:7]=[C:6]([F:42])[CH:5]=1.[CH3:43][N:44]1[C:48](B2OC(C)(C)C(C)(C)O2)=[CH:47][CH:46]=[N:45]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:41][C:38]1[CH:39]=[CH:40][C:35]([CH:13]([C:9]2[C:8]3[CH:7]=[C:6]([F:42])[CH:5]=[C:4]([C:48]4[N:44]([CH3:43])[N:45]=[CH:46][CH:47]=4)[C:12]=3[S:11][CH:10]=2)[C@@H:14]([C:19]2[CH:34]=[CH:33][C:22]([C:23]([NH:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:24])=[CH:21][CH:20]=2)[CH2:15][CH2:16][CH2:17][CH3:18])=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58513014HCID 58513014, compound

Product 1

HCID 46853082HCID 46853082, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Dioxane (1.4 mL) and LiOH (2.0 M in water, 0.68 mL, 1.36 mmol) were added to a mixture of ethyl N-(4-{(1S)-1-[(7-bromo-5-fluoro-1-benzothien-3-yl)(4-chlorophenyl)methyl]pentyl}benzoyl)-β-alaninate (23.0 mg, 0.036 mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (11.0 mg, 0.053 mmol), and PdCl2(dppf) (0.029 g, 0.036 mmol) in a sealed microwave vial under a nitrogen atmosphere. The mixture was degassed then irradiated in a microwave reactor at 80° C. for 15 minutes. The mixture was acidified with acetic acid then extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, then concentrated. The resulting residue was purified by preparative reverse-phase HPLC eluting with acetonitrile/water+0.1% TFA. The resulting material was further purified by silica gel chromatography eluting with 5% MeOH/DCM+0.5% acetic acid to afford the title compound. 1H NMR (500 MHz, CDCl3): δ 7.57 (br, 3H); 7.29-7.37 (m, 6H); 7.23 (d, J=6 Hz, 2H); 6.94 (d, J=7 Hz, 1H); 6.86 (br, 1H); 6.40 (br, 1H); 4.47 (d, J=11 Hz, 1H); 3.71 (br, 3H); 3.62 (br, 2H); 3.43 (t, J=9.5 Hz, 1H); 2.59 (br, 2H); 1.45-1.52 (m, 2H); 1.13-1.16 (m, 1H); 1.04-1.06 (m, 1H); 0.88-1.00 (m, 2H); 0.68 (t, J=6.5 Hz, 3H). LC1: 3.99 min. (M+H)+ 618.

Workup

  1. customThe mixture was degassed
  2. customthen irradiated in a microwave reactor at 80° C. for 15 minutes
  3. extractionthen extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by preparative reverse-phase HPLC
  8. washeluting with acetonitrile/water+0.1% TFA
  9. customThe resulting material was further purified by silica gel chromatography
  10. washeluting with 5% MeOH/DCM+0.5% acetic acid

Sources & evidence

ORD record
ord-54bd2d07db1d4a6d952712c8a5952808
Source dataset
uspto-grants-2016_06
Patent number
US09359339B2

Reaction notes

Loading…