tert-Butyl carbamate → HCID 86669027, compound

HRID 2366311Notes

Reaction equation

HRID 2366311 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([F:17])=[CH:15][C:14](I)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[C:20](=[O:27])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH2:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:12]1[CH:13]=[C:14]([NH:21][C:20](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:15]=[C:16]([F:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1

Participants

8

Reactant 3

HCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86669028HCID 86669028, compound

Product 1

HCID 86669027HCID 86669027, compoundYield 78.9%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-2-(2-chloro-6-fluoro-4-iodo-phenyl)thiazolo[5,4-c]pyridine (715 mg, 1.682 mmol), tert-butyl carbamate (394 mg, 3.365 mmol), Pd2(dba)3 (77 mg, 0.084 mmol), and XantPhos (97 mg, 0.168 mmol) in toluene (17 mL) and K3PO4 (2.65 mL, 1.27 M) was heated at 90° C. under nitrogen for 20 hours. The reaction mixture was diluted with water, extracted with EtOAc (2×). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane) to give the title compound (550 mg, 78.9% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J=5.6 Hz, 1H), 7.95 (d, J=5.6 Hz, 1H), 7.46-7.33 (m, 2H), 6.70 (s, 1H), 1.55 (s, 9H). LCMS (ESI) m/z 414.1 [M+H+].

Workup

  1. extractionextracted with EtOAc (2×)
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane)

Sources & evidence

ORD record
ord-0d8962f89040469b829c47b82f7fc0f9
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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