Cesium carbonate → HCID 86762155, compound

HRID 1907419Notes

Reaction equation

HRID 1907419 reaction equation
Br[C:2]1[C:3]([F:26])=[CH:4][C:5]([F:25])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]3)[CH:7]=1.BrC1C(F)=CC(F)=C(C=1)C=O.F[C:39]1[CH:44]=[CH:43][C:42]([N+]([O-])=O)=[CH:41][C:40]=1[C@@:48]12OCC[C@@H]1CS[C:50](NC(=O)OC(C)(C)C)=[N:49]2.FC1C=CC([N+]([O-])=O)=CC=1C=O.BrC1C(F)=CC(F)=C([C@@]23OCC[C@@H]2CSC(NC(=O)OC(C)(C)C)=N3)C=1.C(C1C=C(B(O)O)C=NC=1)#CC.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:25][C:5]1[CH:4]=[C:3]([F:26])[C:2]([C:40]2[CH:48]=[N:49][CH:50]=[C:42]([C:43]#[C:44][CH3:39])[CH:41]=2)=[CH:7][C:6]=1[C@:8]12[O:16][CH2:15][CH2:14][C@H:13]1[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]2

Participants

12

Reactant 7

HCID 10796Cesium carbonateHCID 27347702-Fluoro-5-nitrobenzaldehydeHCID 222607695-Bromo-2,4-difluorobenzaldehydeHCID 574164825-(1-Propynyl)pyridine-3-boronic Acid (contains varying amounts of Anhydride)HCID 86762156HCID 86762156, compoundHCID 86762157HCID 86762157, compoundHCID 86762158HCID 86762158, compound

Product 1

HCID 86762155HCID 86762155, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

(±)-tert-butyl (4aR,7aR)-7a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate was made from 5-bromo-2,4-difluorobenzaldehyde in the same fashion as (±)-tert-butyl (4aS,7aS)-7a-(2-fluoro-5-nitrophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate from 2-fluoro-5-nitrobenzaldehyde (Step A to Step F, Preparation 1). A mixture of (±)-tert-butyl (4aS,7aS)-7a-(5-bromo-2,4-difluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate (60 mg), 5-(prop-1-ynyl)pyridin-3-ylboronic acid (Preparation 9, 86 mg), cesium carbonate (174 mg), and PdCl2(PPh3)2 (19 mg) in DME (0.44 mL), EtOH (0.22 mL) and water (0.22 mL) was heated at 100° C. for 10 min in a microwave, and the crude reaction mixture was subjected to preparative HPLC eluting with 0-100% B (A: 95% H2O/5% MeCN, 10 mM NH4OAc; B: 5% H2O/95% MeCN, 10 mM NH4OAC over 12 min period to give the title compound as a white foam (22 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.65 (br. s., 1H), 7.82 (s, 1H), 7.65 (t, J=8.7 Hz, 1H), 7.00 (t, J=10.3 Hz, 1H), 4.23-4.13 (m, 1H), 4.12-4.04 (m, 1H), 3.30 (d, J=11.5 Hz, 1H), 3.00-2.83 (m, 2H), 2.47-2.35 (m, 1H), 2.28-2.16 (m, 1H), 2.14-2.10 (m, 3H), 1.50 (s, 9H). MS (M+H)+: 486.3.

Workup

  1. customthe crude reaction mixture
  2. washeluting with 0-100% B (A: 95% H2O/5% MeCN, 10 mM NH4OAc

Sources & evidence

ORD record
ord-7ce3d54279d24644929180ba4dafe5c2
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

Loading…