Hydrochloric Acid → HCID 67111778, compound

HRID 1177619Notes

Reaction equation

HRID 1177619 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH:10]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[S:23][C:24]3[C:29]([N:30]=2)=[CH:28][CH:27]=[C:26]([C:31]2([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:33][CH2:32]2)[N:25]=3)=[C:18]([F:40])[CH:17]=1)[C:11]([OH:13])=[O:12].[CH3:41][C:42]([O:45][C:46](O[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:47])([CH3:44])[CH3:43].Cl>C1COCC1.O.CCOC(C)=O>[C:42]([O:45][C:46]([NH:9][C@H:10]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[S:23][C:24]3[C:29]([N:30]=2)=[CH:28][CH:27]=[C:26]([C:31]2([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:33][CH2:32]2)[N:25]=3)=[C:18]([F:40])[CH:17]=1)[C:11]([OH:13])=[O:12])=[O:47])([CH3:44])([CH3:43])[CH3:41].[C:52]([O:51][C:49]([NH:9][C@@H:10]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[S:23][C:24]3[C:29]([N:30]=2)=[CH:28][CH:27]=[C:26]([C:31]2([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:33][CH2:32]2)[N:25]=3)=[C:18]([F:40])[CH:17]=1)[C:11]([OH:13])=[O:12])=[O:50])([CH3:53])([CH3:54])[CH3:55]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 67111648HCID 67111648, compound

Product 2

HCID 67111778HCID 67111778, compoundHCID 68635898HCID 68635898, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (0.0967 mL, 0.695 mmol) was added to a slurry of (rac)-2-amino-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)butanoic acid hydrochloride (0.153 g, 0.316 mmol) in THF (5.00 mL, 61.7 mmol) and WATER (5.00 mL, 278 mmol). The reaction mixture was cooled in an ice bath, and a solution of Boc2O (0.117 g, 0.537 mmol) in THF 2 mL was added dropwise, and the solution was then stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and EtOAc, pH was adjusted to 5 with 1 N aq. HCl, and the aqueous layer was extracted with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated in vacuo, and the residue purified by chiral SFC (Column: Chiralpak AS-H (21×250 mm, 5 um); A: Liquid CO2; B: Methanol; Isocratic: 70:30 (A:B); Flow Rate: 70 mL/min) to give separately (R)-2-(tert-butoxycarbonylamino)-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)phenyl)butanoic acid and (S)-2-(tert-butoxycarbonylamino)-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)butanoic acid. MS (ESI) m/z: calculated: 547.2; Observed: 548.1 (M++1).

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by chiral SFC (Column

Sources & evidence

ORD record
ord-887664785de04783b4ffa3db720adffe
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…