HCID 89689847, compound → HCID 89689719, compound

HRID 877552Notes

Reaction equation

HRID 877552 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[O:18][C:19]([CH:27]([CH3:29])[CH3:28])=[C:20](C(OCC)=O)[N:21]=4)=[C:13]([NH:30][CH:31]([CH3:33])[CH3:32])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C[Mg]Br>O1CCCC1>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[O:18][C:19]([CH:27]([CH3:29])[CH3:28])=[C:20]([C:19]([OH:18])([CH3:27])[CH3:20])[N:21]=4)=[C:13]([NH:30][CH:31]([CH3:33])[CH3:32])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 89689847HCID 89689847, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 89689719HCID 89689719, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate (29) (150 mg, 0.34 mmol) in dry Tetrahydrofuran (10 mL) was added methyl magnesium bromide (2.132 mmol) (3.0 M in diethyl ether) at −78° C. Reaction mixture was allowed to warm up to 25° C. over 2 h. The reaction mixture was cooled to 0° C. and quenched by the addition of saturated aqueous NH4Cl solution dropwise. Extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated to get the crude product, which was purified by flash column using ethyl acetate/hexanes as eluent to furnish 2-(2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-isopropyloxazol-4-yl)propan-2-ol. 1H NMR: 400 MHz, DMSO-d6: δ 1.26-1.27 (m, 13H), 1.48 (s, 6H), 3.63-3.71 (m, 2H), 5.06 (s, 1H), 6.13 (s, 1H), 7.57 (dd, J=2.00, 8.80 Hz, 1H), 7.95 (d, J=8.80 Hz, 1H), 8.28 (d, J=6.80 Hz, 1H), 8.51 (s, 1H), 8.75 (d, J=2.00 Hz, 1H), 9.15 (s, 1H), 9.28 (s, 1H). LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.842 min; LCMS (ES-API), m/z 452.2 (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: 7.608 min; Purity: 97.8%.

Workup

  1. customReaction mixture
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched by the addition of saturated aqueous NH4Cl solution dropwise
  4. extractionExtracted with ethyl acetate
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto get the crude product, which
  9. customwas purified by flash column

Sources & evidence

ORD record
ord-91d073ff2eb84e85baee230e30e27337
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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