Water → 4-{7-[4-(1,1-Dioxo-thiomorpholin-4-ylmethyl)-3,5-difluoro-phenyl]-benzooxazol-2-ylamino}-2,N,N-trimethyl-benzamide

HRID 469827Notes

Reaction equation

HRID 469827 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([NH:11][C:12]3[CH:22]=[CH:21][C:15]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[C:14]([CH3:23])[CH:13]=3)=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[F:24][C:25]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[C:36]([F:49])[C:26]=1[CH2:27][N:28]1[CH2:33][CH2:32][S:31](=[O:35])(=[O:34])[CH2:30][CH2:29]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:35]=[S:31]1(=[O:34])[CH2:32][CH2:33][N:28]([CH2:27][C:26]2[C:36]([F:49])=[CH:37][C:38]([C:2]3[C:10]4[O:9][C:8]([NH:11][C:12]5[CH:22]=[CH:21][C:15]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[C:14]([CH3:23])[CH:13]=5)=[N:7][C:6]=4[CH:5]=[CH:4][CH:3]=3)=[CH:39][C:25]=2[F:24])[CH2:29][CH2:30]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 593928004-[2,6-Difluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-thiomorpholine 1,1-dioxidHCID 674578214-(7-bromo-benzooxazol-2-ylamino)-2,N,N-trimethyl-benzamide

Product 1

HCID 591443304-{7-[4-(1,1-Dioxo-thiomorpholin-4-ylmethyl)-3,5-difluoro-phenyl]-benzooxazol-2-ylamino}-2,N,N-trimethyl-benzamide

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 0.1 g (0.267 mmol) 4-(7-bromo-benzooxazol-2-ylamino)-2,N,N-trimethyl-benzamide, 0.114 g (0.294 mmol) 4-[2,6-difluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-thiomorpholine 1,1-dioxid and 174 mg K3PO4 are dissolved in 5 ml 1,2-dimethoxy-ethane, water (0.1 ml) is added and a stream of argon is bubbled through the mixture in order to exclude oxygen from the reaction mixture. Tetrakis (triphenylphosphine) palladium (0.0095 g, 0.0082 mmol) is added and the reaction mixture is stirred at 100° C. for 8 h. After that the reaction mixture is poured on water and extracted 3× with EtOAc. The combined organic layers are washed with water and saturated NaCl solution, dried over MgSO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography (silicagel, EtOAc), followed by recrystallisation diethylether/methanol to afford the title compound as white crystals. Rt=2.13 min (Waters Symmetry C8, 2.1×50 mm, detection 210-250 nM, 5% to 100% CH3CN in H2O in 2 min+0.05% TFA, flow rate 1.0 ml/min); MS: 555 (M+1)+.

Workup

  1. customa stream of argon is bubbled through the mixture in order
  2. additionAfter that the reaction mixture is poured on water
  3. extractionextracted 3× with EtOAc
  4. washThe combined organic layers are washed with water and saturated NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe residue is purified by chromatography (silicagel, EtOAc)
  9. customfollowed by recrystallisation diethylether/methanol

Sources & evidence

ORD record
ord-e1317406ee524d3f8d3c856d24ed7f80
Source dataset
uspto-grants-2014_01
Patent number
US08629168B2

Reaction notes

Loading…