Trifluoroacetic acid → (1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 2242425Notes

Reaction equation

HRID 2242425 reaction equation
C(O[C:6]([C@@H:8]1[CH2:12][C@H:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:15]=2)[CH2:10][C@H:9]1[C:32](=[O:44])[NH:33][C@:34]1([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:7])(C)(C)C.C([SiH]([CH2:50][CH3:51])CC)C.C(O)(C(F)(F)F)=O.C(OC(=O)[NH:65][C@H:66]([C:71](=[O:84])[NH:72][C@@H:73](C1CCCCC1)[C:74](=[O:77])[NH:75][CH3:76])[C:67]([CH3:70])([CH3:69])[CH3:68])(C)(C)C.CN(C(ON1N=N[C:96]2[CH:97]=[CH:98]C=N[C:95]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OC([C@@H]1C[C@@H](O)C[C@H]1C(=O)N[C@]1(C(OCC)=O)C[C@H]1C=C)=O)(C)(C)C>C(Cl)Cl>[CH2:42]([O:41][C:39]([C@@:34]1([NH:33][C:32]([C@@H:9]2[CH2:10][C@@H:11]([O:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:15]=3)[CH2:12][C@H:8]2[C:6](=[O:7])[NH:65][C@H:66]([C:71](=[O:84])[NH:72][C@@H:73]([CH:51]2[CH2:50][CH2:98][CH2:97][CH2:96][CH2:95]2)[C:74](=[O:77])[NH:75][CH3:76])[C:67]([CH3:69])([CH3:70])[CH3:68])=[O:44])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:40])[CH3:43]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57892933{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl esterHCID 59165438(1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl esterHCID 59204175(1R,2R,4R)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid tert-butyl ester2×

Product 1

HCID 59204178(1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 35 (30 mg, 0.050 mmol) in methylene chloride (1.5 mL) were added triethylsilane (21 □L, 0.132 mmol) and TFA (1.5 mL). The mixture was stirred for 2 h at room temperature and was then evaporated and coevaporated with toluene. The amine 38 (1.3 eq) was deprotected in the same manner as compound 35 and was then coupled to deprotected compound 35 using the same HATU coupling conditions as in the synthesis of 34. The crude product was extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification using HPLC (MeOH/water 9:1+0.2% triethylamine) provided compound 39 (30 mg, 74%) as a colorless solid.

Workup

  1. customwas then evaporated
  2. extractionThe crude product was extracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification

Sources & evidence

ORD record
ord-3d7bd8536cd844a1893f40922ebdb776
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

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