Hydrochloric Acid → HCID 67111698, compound

HRID 1177618Notes

Reaction equation

HRID 1177618 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[S:22][C:23]3[C:28]([N:29]=2)=[CH:27][CH:26]=[C:25]([C:30]2([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:32][CH2:31]2)[N:24]=3)=[C:17]([F:39])[CH:16]=1)[C:11]([OH:13])=[O:12].[CH3:40][C:41]([O:44][C:45](O[C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[O:46])([CH3:43])[CH3:42].Cl>C1COCC1.O.CCOC(C)=O>[C:41]([O:44][C:45]([NH:9][C@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[S:22][C:23]3[C:28]([N:29]=2)=[CH:27][CH:26]=[C:25]([C:30]2([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:32][CH2:31]2)[N:24]=3)=[C:17]([F:39])[CH:16]=1)[C:11]([OH:13])=[O:12])=[O:46])([CH3:43])([CH3:42])[CH3:40].[C:51]([O:50][C:48]([NH:9][C@@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[S:22][C:23]3[C:28]([N:29]=2)=[CH:27][CH:26]=[C:25]([C:30]2([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:32][CH2:31]2)[N:24]=3)=[C:17]([F:39])[CH:16]=1)[C:11]([OH:13])=[O:12])=[O:49])([CH3:52])([CH3:53])[CH3:54]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 67111851HCID 67111851, compound

Product 2

HCID 67111698HCID 67111698, compoundHCID 67112101HCID 67112101, compound

Reagents, catalysts & solvents 3

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

Procedure

Triethylamine (0.0716 mL, 0.515 mmol) was added to a slurry of 2-amino-3-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)propanoic acid hydrochloride (0.110 g, 0.234 mmol) in THF (5.00 mL) and water (5.00 mL). The reaction mixture was cooled in ice bath and a solution of Boc2O (0.0868 g, 0.398 mmol) in THF (1 mL) was addded dropwise then the solution was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and EtOAc, pH was adjusterd to 5 with 1 N HCl, and the aq. layer was extracted with EtOAc; the combined organics were dried over MgSO4, filtered, and concentrated in vacuo. The material was purified by chiral SFC (Column: Chiralpak AD-H (21×250 mm, 5 micron); A: Liquid CO2; B: Isopropanol (0.2% DEA); Isocratic: 75:25 (A:B); Flow Rate: 70 mL/min; Outlet Pressure: 100 bar) to give (R)-2-(tert-butoxycarbonylamino)-3-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)propanoic acid and (S)-2-(tert-butoxycarbonylamino)-3-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)propanoic acid. MS (ESI) m/z: calculated: 533.2; Observed: 534.1 (M++1).

Workup

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

Sources & evidence

ORD record
ord-104acc6b1e0b42ad8f9bb8a362bfede0
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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