Diisopropylethylamine → (2S,4S)-tert-butyl 2-(hex-5-enyl(methyl)carbamoyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1-carboxylate

HRID 420085Notes

Reaction equation

HRID 420085 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([O:13][C:14]2[C:23]3[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:27]3[S:28][CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:31]=3)[CH:15]=2)[CH2:10][C@H:9]1[C:36](O)=[O:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH3:72][NH:73][CH2:74][CH2:75][CH2:76][CH2:77][CH:78]=[CH:79]C.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:74]([N:73]([CH3:72])[C:36]([C@@H:9]1[CH2:10][C@H:11]([O:13][C:14]2[C:23]3[C:18](=[C:19]([CH3:26])[C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:27]3[S:28][CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:31]=3)[CH:15]=2)[CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:37])[CH2:75][CH2:76][CH2:77][CH:78]=[CH2:79]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66650507(2S,4S)-1-(tert-butoxycarbonyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-2-carboxylic acidHCID 131729112n-Methylhept-5-en-1-amine tosylate salt

Product 1

HCID 66650484(2S,4S)-tert-butyl 2-(hex-5-enyl(methyl)carbamoyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Compound 125 (21.33 g) was dissolved in anhydrous DMF (48 mL) at room temperature. O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.25 eq.) was added at room temperature and the reaction mixture was stirred for 10 min. Compound 32b (1.1 eq.) was added and the reaction mixture was stirred for additional 10-15 min. After cooling to 5° C., diisopropylethylamine (3 eq.) was added. After warming to room temperature for 1 hr, the reaction mixture was diluted with ethyl acetate, washed with brine and ammonium chloride, dried over Na2SO4, and concentrated under vacuum to give crude 126 (22.09 g) as an orange foam. The crude product was crystallized from ethyl acetate and heptane to give compound 126 (20.8 g) as an off-white powder in 90% yield and 99% purity.

Workup

  1. stirringthe reaction mixture was stirred for additional 10-15 min
  2. temperatureAfter warming to room temperature for 1 hr
  3. washwashed with brine and ammonium chloride
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5f81fda4b65a477a93e98ac8643d7272
Source dataset
uspto-grants-2012_01
Patent number
US08093379B2

Reaction notes

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