2-(Methylamino)ethanol → HCID 54670800, compound

HRID 408008Notes

Reaction equation

HRID 408008 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:31])[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([O:19][C:20]4[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][C:21]=4[F:29])[C:15]3=[O:30])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH3:65][NH:66][CH2:67][CH2:68][OH:69]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([F:31])[C:5]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([O:19][C:20]4[CH:28]=[CH:27][C:23]([C:24]([N:66]([CH2:67][CH2:68][OH:69])[CH3:65])=[O:26])=[CH:22][C:21]=4[F:29])[C:15]3=[O:30])[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67469835(S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

Product 1

HCID 54670800HCID 54670800, compoundYield 29.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (Example 153, Step B; 0.1 g, 0.22 mmol) in DMF (2 mL) was added HATU (0.17 g, 0.44 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.12 mL, 0.66 mmol) and the reaction was stirred for 20 minutes at ambient temperature. 2-(Methylamino)ethanol (0.050 g, 0.66 mmol) was added, and the reaction was stirred for 2 hours at ambient temperature. The reaction was diluted with EtOAc (30 mL) and washed with HCl (1 N, 10 mL), NaOH (1 N, 10 mL), water (10 mL), and brine (10 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified by reverse phase HPLC. The combined fractions were diluted with EtOAc (50 mL) and washed with 1 N NaOH (10 mL), water (10 mL), and brine (10 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum to give (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluoro-N-(2-hydroxyethyl)-N-methylbenzamide (0.033 g, 0.064 mmol, 29% yield). Mass spectrum (apci) m/z=509.0 (M+H).

Workup

  1. stirringthe reaction was stirred for 2 hours at ambient temperature
  2. washwashed with HCl (1 N, 10 mL), NaOH (1 N, 10 mL), water (10 mL), and brine (10 mL)
  3. dry with materialthe combined organic phases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude material was purified by reverse phase HPLC
  7. additionThe combined fractions were diluted with EtOAc (50 mL)
  8. washwashed with 1 N NaOH (10 mL), water (10 mL), and brine (10 mL)
  9. dry with materialthe combined organic phases were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ca8f5216ec1d46678a9217db3f7a89dc
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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