Diisopropylethylamine → 3-bromo-N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-1-trityl-1H-indazole-5-carboxamide

HRID 1467339Notes

Reaction equation

HRID 1467339 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:35](O)=[O:36])[CH:33]=2)[N:28]([C:38]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:27]=1.[F:57][C:58]1[CH:72]=[CH:71][CH:70]=[C:69]([F:73])[C:59]=1[CH2:60][CH:61]1[CH2:66][N:65]([CH3:67])[CH2:64][CH:63]([NH2:68])[CH2:62]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:35]([NH:68][CH:63]3[CH2:62][CH:61]([CH2:60][C:59]4[C:69]([F:73])=[CH:70][CH:71]=[CH:72][C:58]=4[F:57])[CH2:66][N:65]([CH3:67])[CH2:64]3)=[O:36])[CH:33]=2)[N:28]([C:38]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:27]=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 679957455-(2,6-Difluorobenzyl)-1-methylpiperidin-3-amineHCID 679965973-bromo-1-trityl-1H-indazole-5-carboxylic acid

Product 1

HCID 679965083-bromo-N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-1-trityl-1H-indazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (3.1 mmol) was added to a suspension of 3-bromo-1-trityl-1H-indazole-5-carboxylic acid (1 g, 2.07 mmol) in DMF (5 mL) and was stirred at room temperature for 15 minutes. A solution of 5-(2,6-difluorobenzyl)-1-methylpiperidin-3-amine (511 mg, 2.13 mmol) in DMF (5 mL) was added to the reaction and followed by diisopropyl ethyl amine (DIEA) (0.72 mL). The mixture was stirred at room temperature for an additional 30 minutes. The reaction was quenched with water (50 mL) and extracted with ethyl acetate (3×100 mL). The extracts were combined, dried using anhydrous sodium sulfate, filtered, and concentrated in vacuum. The crude product was progressed to the next step without purification.

Workup

  1. stirringThe mixture was stirred at room temperature for an additional 30 minutes
  2. customThe reaction was quenched with water (50 mL)
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customThe crude product was progressed to the next step without purification

Sources & evidence

ORD record
ord-03479b2c77af418b84cb2c38b33e477d
Source dataset
uspto-grants-2015_04
Patent number
US08999957B2

Reaction notes

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