Hydrochloric Acid → (S)-2-{[(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}-pentanoic acid tert-butyl ester

HRID 2242430Notes

Reaction equation

HRID 2242430 reaction equation
CO[C:3]([C@@H:5]1[CH2:9][C@H:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:12]=2)[CH2:7][C@H:6]1[C:29](=[O:42])[NH:30][C@H:31]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:32][CH2:33][CH3:34])=[O:4].[Li+].[OH-].Cl.C(OC(=O)[NH:52][C@H:53]([C:58](=[O:71])[NH:59][C@@H:60]([CH:65]1[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]1)[C:61](=[O:64])[NH:62][CH3:63])[C:54]([CH3:57])([CH3:56])[CH3:55])(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=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>O1CCOCC1.O.CN(C=O)C>[C:38]([O:37][C:35](=[O:36])[C@@H:31]([NH:30][C:29]([C@@H:6]1[CH2:7][C@@H:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:12]=2)[CH2:9][C@H:5]1[C:3](=[O:4])[NH:52][C@H:53]([C:58](=[O:71])[NH:59][C@@H:60]([CH:65]1[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70]1)[C:61](=[O:64])[NH:62][CH3:63])[C:54]([CH3:56])([CH3:57])[CH3:55])=[O:42])[CH2:32][CH2:33][CH3:34])([CH3:40])([CH3:41])[CH3:39]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 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 59204183(1R,2R,4R)-2-((S)-1-tert-Butoxycarbonyl-butylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid methyl ester

Product 1

HCID 59204189(S)-2-{[(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}-pentanoic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

Compound 43 (38 mg, 0.066 mmol) was dissolved in dioxane/water 1:1 (4 mL) and the solution was cooled to 0° C. and 1 M LiOH (132 ul, 0.132 mmol) was added. The temperature was raised to room temperature and the solution was stirred for 2 hours after which it was neutralized by addition of 1M HCl and evaporated and coevaporated with toluene. The residue and deprotected amine 38 (1.1 eq) was dissolved in DMF and coupled using the standard HATU coupling conditions as in the synthesis of compound 34. The crude product was extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification with HPLC (MeOH/water 9:1+0.2% TEA) provided compound 44 (44 mg, 81%) as a colorless solid.

Workup

  1. temperatureThe temperature was raised to room temperature
  2. customevaporated
  3. extractionThe crude product was extracted with EtOAc
  4. washwashed with brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification with HPLC (MeOH/water 9:1+0.2% TEA)

Sources & evidence

ORD record
ord-13e3031341644732949a319c87fbb654
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

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