Sodium Carbonate → HCID 71667709, compound

HRID 877588Notes

Reaction equation

HRID 877588 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C:13]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[O:14])=[N:10][N:9]=2)=[C:4]([NH:21][CH:22]([CH3:24])[CH3:23])[CH:3]=1.[NH2:25][C:26]1[CH:34]=[CH:33][C:29]2[N:30]=[CH:31][S:32][C:28]=2[CH:27]=1.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.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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].O>[S:32]1[C:28]2[CH:27]=[C:26]([NH:25][C:2]3[N:7]=[CH:6][C:5]([C:8]4[O:12][C:11]([C:13]([N:15]5[CH2:20][CH2:19][O:18][CH2:17][CH2:16]5)=[O:14])=[N:10][N:9]=4)=[C:4]([NH:21][CH:22]([CH3:24])[CH3:23])[CH:3]=3)[CH:34]=[CH:33][C:29]=2[N:30]=[CH:31]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 682886-AminobenzothiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89690940HCID 89690940, compound

Product 1

HCID 71667709HCID 71667709, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

To solution of (5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)(morpholino)methanone in dioxane (5 mL): H2O (1 mL), 6-amino benzothiazole (1.2 equiv.), xanthphos (0.5 equiv.) and Na2CO3 (3 equiv.) were added and degassed for 10 min. To the reaction mixture Pd2(dba)3 (0.5 equiv.) was added and degassed again for 10 min. It was then heated at 115° C., overnight. The reaction mass was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel (230-400 mesh) and MeOH: CHCl3 as eluent. It was further purified by prep HPLC to afford the title compound. 1H NMR: 400 MHz, CD3OD: δ 1.31-1.38 (m, 6H), 3.81-3.86 (m, 7H), 4.19-4.22 (m, 2H), 6.19 (s, 1H), 7.57 (dd, J=2.00, 8.60 Hz, 1H), 7.66-7.68 (m, 1H), 7.99 (d, J=8.80 Hz, 1H), 8.48 (d, J=2.00 Hz, 1H), 8.63 (s, 1H), 9.10 (s, 1H). LC/MS: XBridge Phe 8, 4.6×30 mm, 3.5 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 1.604 min; LCMS (ES-API), m/z 463.8 (M−H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 6.224 min; Purity: 98.3%.

Workup

  1. customdegassed for 10 min
  2. customdegassed again for 10 min
  3. temperatureThe reaction mass was cooled
  4. filtrationfiltered through small pad of celite
  5. customThe filtrate obtained
  6. concentrationwas concentrated
  7. customto provide crude material
  8. customThe crude material was purified by column chromatography through silica gel (230-400 mesh) and MeOH
  9. customIt was further purified by prep HPLC

Sources & evidence

ORD record
ord-59873f2dbb5948babec36b6542b00f07
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

Loading…