Trifluoroacetic acid → 3-Methoxy-pyrrolidine-3-carboxylic acid [3-(2-methoxy-pyridin-4-yl)-1H-indazol-5-yl]-amide

HRID 1020949Notes

Reaction equation

HRID 1020949 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C:10]([O:52][CH3:53])([C:13](=[O:51])[NH:14][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:19]=[C:18]3[C:43]2[CH:48]=[CH:47][N:46]=[C:45]([O:49][CH3:50])[CH:44]=2)[CH2:9]1)=O)(C)(C)C.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:50][O:49][C:45]1[CH:44]=[C:43]([C:18]2[C:17]3[C:21](=[CH:22][CH:23]=[C:15]([NH:14][C:13]([C:10]4([O:52][CH3:53])[CH2:11][CH2:12][NH:8][CH2:9]4)=[O:51])[CH:16]=3)[NH:20][N:19]=2)[CH:48]=[CH:47][N:46]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 673434733-Methoxy-3-[3-(2-methoxy-pyridin-4-yl)-1-trityl-1H-indazol-5-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673452223-Methoxy-pyrrolidine-3-carboxylic acid [3-(2-methoxy-pyridin-4-yl)-1H-indazol-5-yl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the stirred solution 3-Methoxy-3-[3-(2-methoxy-pyridin-4-yl)-1-trityl-1H-indazol-5-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 7BV (2.95 g, 4.16 mmole) in DCM (50 mL) at r.t. was added triethylsilane (1.00 ml, 6.24 mmole) followed by TFA (10 mL). The mixture was stirred at r.t. under dry N2 gas for 4-5 hours. The mixture was evaporated to dryness and co-evaporated with dry toluene (2×75 mL). The resulting crude solid was purified on RediSep 120 g cartridge eluting with 2.5%-6% 2M NH3-MeOH/CH2Cl2 to yield an off-white solid 8BV (1.23 g, 80%).

Workup

  1. customThe mixture was evaporated to dryness and co-evaporated with dry toluene (2×75 mL)
  2. customThe resulting crude solid was purified on RediSep 120 g cartridge
  3. washeluting with 2.5%-6% 2M NH3-MeOH/CH2Cl2
  4. customto yield an off-white solid 8BV (1.23 g, 80%)

Sources & evidence

ORD record
ord-5325f27f4a95453fb81f546b2185e492
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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