Diisopropylethylamine → N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-4-methyl-2-morpholinecarboxamide

HRID 42256Notes

Reaction equation

HRID 42256 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][O:6][CH:5]([C:9]([OH:11])=O)[CH2:4]1.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>[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]([CH:5]4[O:6][CH2:7][CH2:8][N:3]([CH3:2])[CH2:4]4)=[O:11])[CH:55]=3)[CH:50]=[CH:51][CH:52]=2)[CH:47]=[CH:46]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 454802174-Methylmorpholine-2-carboxylic acid hydrochlorideHCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Product 1

HCID 44540403N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-4-methyl-2-morpholinecarboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Methyl-2-morpholinecarboxylic acid hydrochloride (40 mg, 0.22 mmol) was treated with HATU (84 mg, 0.22 mmol) in DMF (0.250 mL) and DIPEA (0.069 mL, 0.40 mmol). The mixture was shaken for five minutes prior to treatment with 6-(1H-indol-4-yl)-1H-indazol-4-amine (25 mg, 0.1 mmol) in DMF (0.25 mL). Reaction mixture was left to stand at room temperature for 18 hrs. Solvent was removed in vacuo and the product re-dissolved in chloroform (0.3 mL) prior to application on to a pre-conditioned (methanol then chloroform) NH2 cartridge (0.5 g). Product was eluted after 2 hr with ethyl acetate/methanol (1:1, 3 mL), and concentrated under a stream of nitrogen using blow down apparatus. Purification by MDAP (Method D) afforded the title compound.

Workup

  1. customReaction mixture
  2. waitwas left
  3. waitto stand at room temperature for 18 hrs
  4. customSolvent was removed in vacuo
  5. dissolutionthe product re-dissolved in chloroform (0.3 mL)
  6. washProduct was eluted after 2 hr with ethyl acetate/methanol (1:1, 3 mL)
  7. concentrationconcentrated under a stream of nitrogen using blow down apparatus
  8. customPurification by MDAP (Method D)

Sources & evidence

ORD record
ord-e1a17f80b77044f189168fe7f2dbb1e1
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Reaction notes

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