Trifluoroacetic acid → Ispinesib

HRID 1743325Notes

Reaction equation

HRID 1743325 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:21]([C:25]1[N:34]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:33](=[O:42])[C:32]2[C:27](=[CH:28][C:29]([Cl:43])=[CH:30][CH:31]=2)[N:26]=1)[CH:22]([CH3:24])[CH3:23])[C:12](=[O:20])[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)(C)(C)C.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl>[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([C@@H:21]([C:25]1[N:34]([CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:33](=[O:42])[C:32]2[C:27](=[CH:28][C:29]([Cl:43])=[CH:30][CH:31]=2)[N:26]=1)[CH:22]([CH3:23])[CH3:24])[C:12](=[O:20])[C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 69518107HCID 69518107, compound

Product 1

HCID 6851740IspinesibYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath was charged with 400.0 g of {3-[[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-(4-methyl-benzoyl)-amino]-propyl}-carbamic acid tert-butyl ester (the compound of Formula 304 prepared, e.g., as described in Example 1.8 or 3.3) and 1500 g of TFA (20 eq) premixed in DCM (6000 g). The mixture was stirred at room temperature for about 6 hours at which time the reaction was determined to be complete by TLC. The reaction vessel was cooled and slowly charged with 4N sodium hydroxide until basic. The resulting solution was washed with brine, dried over sodium sulfate and concentrated under reduced pressure at 35° C. to give the title compound of Formula I, (R)-N-(3-amino-propyl)-N-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinalolin-2-yl)-2-methyl-propyl]-4-methyl-benzamide, 325 g (97% yield) as a white foam solid.

Workup

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath
  2. customprepared
  3. temperatureThe reaction vessel was cooled
  4. washThe resulting solution was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure at 35° C.

Sources & evidence

ORD record
ord-b299068ec0854a27be01a0c602c4c940
Source dataset
uspto-grants-2006_03
Patent number
US07009049B2

Reaction notes

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