HCID 58046450, compound → HCID 67122893, compound

HRID 2046421Notes

Reaction equation

HRID 2046421 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7](Cl)=[O:8])=[N:4][C:3]=1[C:10]1[N:14]2[N:15]=[CH:16][CH:17]=[CH:18][C:13]2=[N:12][CH:11]=1.C(OC(=O)[NH:25][C@H:26]1[CH2:31][CH2:30][CH2:29][C:28]([F:33])([F:32])[C@@H:27]1[NH2:34])(C)(C)C>ClCCl>[NH2:25][C@@H:26]1[C@@H:27]([NH:34][C:7]([C:5]2[S:6][C:2]([Cl:1])=[C:3]([C:10]3[N:14]4[N:15]=[CH:16][CH:17]=[CH:18][C:13]4=[N:12][CH:11]=3)[N:4]=2)=[O:8])[C:28]([F:33])([F:32])[CH2:29][CH2:30][CH2:31]1

Participants

4

Reactant 2

HCID 58046450HCID 58046450, compoundHCID 59603843HCID 59603843, compound

Product 1

HCID 67122893HCID 67122893, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Chloro-4-(imidazo[1,2-b]pyridazin-3-yl)-1,3-thiazole-2-carbonyl chloride (59.5 mg, 0.199 mmol) and tert-butyl[(1S,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (54.8 mg, 0.219 mmol) were dissolved in dry dichloromethane (3 mL). The reaction mixture was left to stir at room temperature for 42 h. After consumption of the starting material, trifluoroacetic acid (2 mL) was added to the reaction mixture and left to stir at room temperature for 2 h. The solution was then concentrated and the residue purified by prep HPLC. The compound was neutralized by taking the fractions and adding an aqueous saturated sodium bicarbonate solution and extracting three times with ethyl acetate. The combined organics were dried with magnesium sulfate, filtered, and concentrated to afford the title compound as a yellow solid. 1H NMR (500 MHz, CD3SOCD3) δ 8.73 (d, 1H); 8.66 (s, 1H); 8.24 (d, 1H); 7.45 (dd, 1H); 4.05 (m, 1H); 2.85 (m, 1H); 2.08 (m, 1H); 1.22-2.08 (m, 6H). LRMS (APCI) calc'd for (C16H15ClF2N6OS) [M+H]+, 413.1. found 413.0.

Workup

  1. waitThe reaction mixture was left
  2. customAfter consumption of the starting material, trifluoroacetic acid (2 mL)
  3. additionwas added to the reaction mixture
  4. waitleft
  5. stirringto stir at room temperature for 2 h
  6. concentrationThe solution was then concentrated
  7. customthe residue purified by prep HPLC
  8. additionadding an aqueous saturated sodium bicarbonate solution
  9. extractionextracting three times with ethyl acetate
  10. dry with materialThe combined organics were dried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-399a748a4c0e4c1993354310b5a8ada4
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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