Hydrochloric Acid → HCID 58949445, compound

HRID 1676396Notes

Reaction equation

HRID 1676396 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O.[NH2:40][C:41]1[CH:74]=[CH:73][C:44]([O:45][C:46]2[CH:51]=[CH:50][N:49]=[C:48]3[CH:52]=[C:53]([C:55]4[CH:56]=[N:57][N:58]([CH:60]5[CH2:65][CH2:64][N:63](C(OC(C)(C)C)=O)[CH2:62][CH2:61]5)[CH:59]=4)[S:54][C:47]=23)=[C:43]([F:75])[CH:42]=1.CCN(C(C)C)C(C)C.Cl>O.CO.CN(C=O)C>[F:75][C:43]1[CH:42]=[C:41]([NH:40][C:15]([C:12]2[C:13](=[O:14])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[CH:10][CH:11]=2)=[O:17])[CH:74]=[CH:73][C:44]=1[O:45][C:46]1[CH:51]=[CH:50][N:49]=[C:48]2[CH:52]=[C:53]([C:55]3[CH:56]=[N:57][N:58]([CH:60]4[CH2:61][CH2:62][NH:63][CH2:64][CH2:65]4)[CH:59]=3)[S:54][C:47]=12

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 67349941HCID 67349941, compound

Product 1

HCID 58949445HCID 58949445, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A round-bottomed flask was charged with 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (Example 104, Step C, 12.9 mg, 0.0549 mmol), EDCI (10.5 mg, 0.0549 mmol), HOBT-H2O (8.41 mg, 0.0549 mmol), tert-butyl 4-(4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (14.0 mg, 0.0275 mmol), Hunig's base (7.10 mg, 0.0549 mmol) and DMF (4 mL). After stirring for 18 hours, the reaction was diluted with water and extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated. Purification by preparative TLC (0.5 mm thickness) 9:1 EtOAc/MeOH gave a band at Rf 0.7 that was isolated, washed from silica with 9:1 EtOAc/MeOH and concentrated to get an oil. HCl (4 mL, 4N dioxane) was added and stirred for 18 hours. The mixture was concentrated to get an orange oil. MeOH (4 mL) was added and the formed precipitate filtered to give (4.2 mg, 23%) as an off white solid. LRMS (esi+) 626 m/z (M+1) detected.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by preparative TLC (0.5 mm thickness) 9:1 EtOAc/MeOH
  6. customgave a band at Rf 0.7 that
  7. customwas isolated
  8. washwashed from silica with 9:1 EtOAc/MeOH
  9. concentrationconcentrated
  10. customto get an oil
  11. stirringstirred for 18 hours
  12. concentrationThe mixture was concentrated
  13. customto get an orange oil
  14. filtrationthe formed precipitate filtered
  15. customto give (4.2 mg, 23%) as an off white solid

Sources & evidence

ORD record
ord-c8d9aa235acc4395b59549ed0b685b42
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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