Diisopropylethylamine → 2-Pyridineacetic acid, hydrochloride (1:1)

HRID 42252Notes

Reaction equation

HRID 42252 reaction equation
[ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[CH3:12][N:13]([C:15]([O:19][N:20]1[N:28]=[N:27][C:22]2[CH:23]=[CH:24][CH:25]=[N:26][C:21]1=2)=[N+:16]([CH3:18])[CH3:17])[CH3:14].[F:29][P-:30]([F:35])([F:34])([F:33])([F:32])[F:31].CCN(C(C)C)C(C)C.[NH:45]1[C:53]2[C:48](=[C:49]([C:54]3[CH:55]=[C:56]([NH2:69])[C:57]4[C:61]([CH:62]=3)=[N:60][N:59](C3CCCCO3)[CH:58]=4)[CH:50]=[CH:51][CH:52]=2)[CH:47]=[CH:46]1>CN(C=O)C>[ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[CH3:18][N:16]([C:15]([O:19][N:20]1[N:28]=[N:27][C:22]2[CH:23]=[CH:24][CH:25]=[N:26][C:21]1=2)=[N+:13]([CH3:14])[CH3:12])[CH3:17].[F:29][P-:30]([F:35])([F:34])([F:33])([F:32])[F:31].[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:69][C:9](=[O:11])[CH2:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=4)[CH:55]=3)[CH:50]=[CH:51][CH:52]=2)[CH:47]=[CH:46]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582679956-(1H-Indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine

Product 3

HCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44540405N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2-(2-pyridinyl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

2-Pyridylacetic acid hydrochloride (0.033 g, 0.191 mmol), HATU (0.084 g, 0.220 mmol) and DIPEA (0.130 ml, 0.764 mmol) were combined in DMF (3 ml) and stirred at 20° C. for 10 minutes. 6-(1H-indol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (0.07 g, 0.20 mmol) was added and the reaction was stirred for 5 h at 20° C. A second batch of 2-pyridylacetic acid hydrochloride (0.033 g, 0.191 mmol), HATU (0.084 g, 0.220 mmol) and DI PEA (0.130 ml, 0.764 mmol) in DMF (3 ml) was prepared and stirred at 20° C. for 10 minutes. It was added to the main reaction mixture and stirred for 3 days (weekend) at 20° C. The reaction mixture was applied to a 5 g NH2-SPE cartridge and eluted with 10% methanol in dichloromethane. The solvent was evaporated and the residue was purified by Mass Directed Auto Prep (Method B) to give the title compound (0.018 g).

Workup

  1. stirringthe reaction was stirred for 5 h at 20° C
  2. stirringstirred at 20° C. for 10 minutes
  3. additionIt was added to the main reaction mixture
  4. stirringstirred for 3 days (weekend) at 20° C
  5. washeluted with 10% methanol in dichloromethane
  6. customThe solvent was evaporated
  7. customthe residue was purified by Mass Directed Auto Prep (Method B)

Sources & evidence

ORD record
ord-5b2c2bcdb42546f29bc363840681bfd3
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Reaction notes

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