Triethylamine → 3-Methoxy-3-[3-(2-methoxy-pyridin-4-yl)-1-trityl-1H-indazol-5-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1020948Notes

Reaction equation

HRID 1020948 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([O:16][CH3:17])([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([NH2:35])[CH:33]=3)[N:28]([C:36]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:27]=2)[CH:23]=[CH:22][N:21]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([O:16][CH3:17])([C:13](=[O:15])[NH:35][C:32]2[CH:33]=[C:34]3[C:29](=[CH:30][CH:31]=2)[N:28]([C:36]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:27]=[C:26]3[C:24]2[CH:23]=[CH:22][N:21]=[C:20]([O:19][CH3:18])[CH:25]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583720003-(2-methoxypyridin-4-yl)-1-trityl-1H-indazol-5-ylamineHCID 673458271-[(Tert-butoxy)carbonyl]-3-methoxypyrrolidine-3-carboxylic acid

Product 1

HCID 673434733-Methoxy-3-[3-(2-methoxy-pyridin-4-yl)-1-trityl-1H-indazol-5-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To the stirred suspension of 3-methoxy-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 6BV (4.16 mmole, crude) in DMF/DCM (25 mL/25 mL), 3-(2-methoxypyridin-4-yl)-1-trityl-1H-indazol-5-ylamine 5BV (2.008 g, 4.16 mmole) and Et3N (2.9 mL, 21 mmole) were added at r.t. under dry N2 gas followed by HATU (3.16 g, 8.32 mmole). The mixture was stirred at r.t. under dry N2 gas overnight. The mixture was partitioned between 1:1 EtOAc and sat. NaHCO3 solution. The organic phase was separated, washed with brine, dried over MgSO4 and evaporated to dryness. The crude solid was purified on RediSep 120 g cartridge eluting with 10-25% EtOAc/Hexanes to yield a brown solid 7BV (2.95 g, 100%).

Workup

  1. customThe mixture was partitioned between 1:1 EtOAc and sat. NaHCO3 solution
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe crude solid was purified on RediSep 120 g cartridge
  7. washeluting with 10-25% EtOAc/Hexanes
  8. customto yield a brown solid 7BV (2.95 g, 100%)

Sources & evidence

ORD record
ord-03ad55f06a0d4c35844b525971cc1e00
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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