Diisopropylethylamine → HCID 44540063, compound

HRID 244731Notes

Reaction equation

HRID 244731 reaction equation
[CH3:1][CH:2]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]([OH:11])=O)[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH:45]1[C:53]2[C:48](=[C:49]([C:54]3[CH:55]=[C:56]([NH2:63])[C:57]4[CH:58]=[N:59][NH:60][C:61]=4[CH:62]=3)[CH:50]=[CH:51][CH:52]=2)[CH:47]=[CH:46]1>CN(C=O)C.C(Cl)Cl.O>[NH:45]1[C:53]2[C:48](=[C:49]([C:54]3[CH:62]=[C:61]4[C:57]([CH:58]=[N:59][NH:60]4)=[C:56]([NH:63][C:9]([C:5]4[N:4]([CH:2]([CH3:1])[CH3:3])[CH:8]=[CH:7][N:6]=4)=[O:11])[CH:55]=3)[CH:50]=[CH:51][CH:52]=2)[CH:47]=[CH:46]1

Participants

8

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 55252644HCID 55252644, compound2×HCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Product 1

HCID 44540063HCID 44540063, compoundYield 18.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 1-(1-methylethyl)-1H-imidazole-2-carboxylic acid (467 mg, contained 50% ethyl 1H-imidazole-2-carboxylate plus inorganic impurities) (now available pure from AKos), HATU (576 mg), and DIPEA (0.793 ml) in DMF (2 ml) was stirred at RT for 10 min. 6-(1H-Indol-4-yl)-1H-indazol-4-amine (188 mg) in DMF (3 ml) was then added and the mixture was stirred at RT. After 3 h at RT, a further quantity of premixed [1-(1-methylethyl)-1H-imidazole-2-carboxylic acid (467 mg), HATU (576 mg), and DIPEA (0.793 ml) in DMF (2 ml)] was added to the reaction mixture and stirring was continued for 2 h at RT. Water (0.5 ml) was added to the reaction mixture, and it was then evaporated to dryness. The residue was partitioned between ethyl acetate (25 ml) and water (10 ml). The phases were separated and the aqueous phase was extracted with further ethyl acetate (2×25 ml). The combined organic extracts were dried over anhydrous sodium sulphate and evaporated to give a brown oily residue which was dissolved in DCM (15 ml) and applied to a 100 g silica SPE cartridge. The cartridge was eluted on a Flashmaster (II) using a gradient of 0-100% ethyl acetate in cyclohexane over 60 min to give a pale brown oil which was dissolved in DCM (5 ml) and applied to a 20 g silica SPE cartridge. The cartridge was eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 40 min followed by 0-20% methanol in ethyl acetate over 15 min to give the title compound (53 mg) as a buff-coloured solid.

Workup

  1. stirringthe mixture was stirred at RT
  2. waitAfter 3 h at RT
  3. additionwas added to the reaction mixture
  4. stirringstirring
  5. waitwas continued for 2 h at RT
  6. customwas then evaporated to dryness
  7. customThe residue was partitioned between ethyl acetate (25 ml) and water (10 ml)
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with further ethyl acetate (2×25 ml)
  10. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
  11. customevaporated
  12. customto give a brown oily residue which
  13. washThe cartridge was eluted on a Flashmaster (II)
  14. customover 60 min
  15. customto give a pale brown oil which
  16. washThe cartridge was eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 40 min
  17. waitfollowed by 0-20% methanol in ethyl acetate over 15 min

Sources & evidence

ORD record
ord-62d7222c7da6455a8581b6368a922a27
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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