Diisopropylethylamine → (2S,4S)-tert-butyl 4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-2-(hex-5-enyl(methyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 420091Notes

Reaction equation

HRID 420091 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]([Cl: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]([CH:32]([CH3:34])[CH3:33])[N:31]=3)[CH:15]=2)[CH2:10][C@H:9]1[C:35]([OH:37])=O)=[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.[CH3:71][NH:72][CH2:73][CH2:74][CH2:75][CH2:76][CH:77]=[CH2:78].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:26][C:19]1[C:20]([O:24][CH3:25])=[CH:21][CH:22]=[C:23]2[C:18]=1[N:17]=[C:16]([C:27]1[S:28][CH:29]=[C:30]([CH:32]([CH3:34])[CH3:33])[N:31]=1)[CH:15]=[C:14]2[O:13][C@@H:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C@H:9]([C:35](=[O:37])[N:72]([CH2:73][CH2:74][CH2:75][CH2:76][CH:77]=[CH2:78])[CH3:71])[CH2:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 46737741N-methylhex-5-en-1-amine 4-methylbenzenesulfonateHCID 66650547(2S,4S)-1-(tert-butoxycarbonyl)-4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)pyrrolidine-2-carboxylic acid

Product 1

HCID 66650750(2S,4S)-tert-butyl 4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-2-(hex-5-enyl(methyl)carbamoyl)pyrrolidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Compound 133 (20.5 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 32a (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 134 (22.09 g) as an orange foam. The crude product was crystallized from ethyl acetate and heptane to give compound 134 (20.55 g) as a white powder in 92% yield and 98% 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-29aaab04a43745c98368930eb2c2b518
Source dataset
uspto-grants-2012_01
Patent number
US08093379B2

Reaction notes

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