Sodium Carbonate → Ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

HRID 595484Notes

Reaction equation

HRID 595484 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:18])=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:12]=2)=[C:4]([NH:19][CH:20]([CH3:22])[CH3:21])[CH:3]=1.[S:23]1[C:27]2[CH:28]=[C:29]([NH2:32])[CH:30]=[CH:31][C:26]=2[N:25]=[CH:24]1.C([O-])([O-])=O.[Na+].[Na+].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>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:23]1[C:27]2[CH:28]=[C:29]([NH:32][C:2]3[N:7]=[CH:6][C:5]([C:8]4[O:9][C:10]([CH3:18])=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:12]=4)=[C:4]([NH:19][CH:20]([CH3:22])[CH3:21])[CH:3]=3)[CH:30]=[CH:31][C:26]=2[N:25]=[CH:24]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 89689612Ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

Product 1

HCID 89689810Ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
115 °C

Procedure

Ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate (28a) (50 mg, 0.15 mmol) was dissolved in 1,4-Dioxane (5 mL):H2O (1 mL), to it benzo[d]thiazol-6-amine (0.15 mmol), Na2CO3 (0.6 mmol) and xanthphos (0.06 mmol) were added and degassed for 10 min. Pd2(dba)3 (0.06 mmol) was added and degassed once again for 15 min and heated at 115° C., overnight. The reaction mass was filtered through a small pad of celite and concentrated the filtrate to remove solvent. The crude material obtained was purified by column chromatography through silica gel and MeOH:CHCl3 as eluent. The material obtained was further purified by preparative TLC to obtain the title compound, ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate. 1H NMR: 400 MHz, DMSO-d6: δ 1.28-1.35 (m, 9H), 2.66 (s, 3H), 3.71-3.72 (m, 1H), 4.30 (q, J=7.20 Hz, 2H), 6.16 (s, 1H), 7.59 (dd, J=2.40, 9.00 Hz, 1H), 7.96 (d, J=8.80 Hz, 1H), 8.10 (d, J=7.20 Hz, 1H), 8.53 (s, 1H), 8.66 (d, J=2.00 Hz, 1H), 9.16 (s, 1H), 9.36 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm, 2.7 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; retention time: 2.127 min; LCMS (ES-API), m/z 438.2 (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: 7.483 min; Purity: 99.7%.

Workup

  1. customdegassed for 10 min
  2. customdegassed once again for 15 min
  3. filtrationThe reaction mass was filtered through a small pad of celite
  4. concentrationconcentrated the filtrate
  5. customto remove solvent
  6. customThe crude material obtained
  7. customwas purified by column chromatography through silica gel and MeOH
  8. customThe material obtained
  9. customwas further purified by preparative TLC

Sources & evidence

ORD record
ord-d60750f513f946cdbfae3db6007dff2c
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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