Diisopropylethylamine → tert-butyl 3-(3-bromo-1-trityl-1H-indazole-5-carboxamido)-4-(3-fluorophenyl)piperidine-1-carboxylate

HRID 1467320Notes

Reaction equation

HRID 1467320 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.[NH2:57][CH:58]1[CH:63]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([F:70])[CH:65]=2)[CH2:62][CH2:61][N:60]([C:71]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:72])[CH2:59]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:57][CH:58]3[CH:63]([C:64]4[CH:69]=[CH:68][CH:67]=[C:66]([F:70])[CH:65]=4)[CH2:62][CH2:61][N:60]([C:71]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:72])[CH2:59]3)=[O:36])[CH:33]=2)[N:28]([C:38]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=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 43810998Tert-butyl 3-amino-4-(3-fluorophenyl)piperidine-1-carboxylateHCID 679965973-bromo-1-trityl-1H-indazole-5-carboxylic acid

Product 1

HCID 67996835tert-butyl 3-(3-bromo-1-trityl-1H-indazole-5-carboxamido)-4-(3-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluoro-phosphate (HATU) (88 mg, 0.231 mmol) was added to a suspension of 3-bromo-1-trityl-1H-indazole-5-carboxylic acid (100 mg, 0.21 mmol) in DMF (0.5 mL) and was stirred at room temperature for 15 minutes. A solution of tert-butyl 3-amino-4-(3-fluorophenyl)piperidine-1-carboxylate (62 mg, 0.21 mmol) in DMF (0.5 mL) was added to the reaction and followed by diisopropyl ethyl amine (DIEA) (0.1 mL). The mixture was stirred at room temperature for an additional 30 minutes. The reaction was quenched with water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracts were combined, dried using anhydrous sodium sulfate, filtered, and concentrated in vacuo. 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 (5 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was progressed to the next step without purification

Sources & evidence

ORD record
ord-d037fb3880ca4e058956fef6522ab5e4
Source dataset
uspto-grants-2015_04
Patent number
US08999957B2

Reaction notes

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