Diisopropylethylamine → HCID 86688118, compound

HRID 408007Notes

Reaction equation

HRID 408007 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](O)=[O:25])=[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.[NH:65]1[CH2:69][CH2:68][C@H:67]([OH:70])[CH2:66]1>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:65]5[CH2:69][CH2:68][C@H:67]([OH:70])[CH2:66]5)=[O:25])=[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 81531DiisopropylethylamineHCID 2733874(3S)-pyrrolidin-3-olHCID 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 86688118HCID 86688118, compoundYield 30.8%

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 (0.10 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. (S)-Pyrrolidin-3-ol (0.058 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 preparative HPLC. The combined fractions were diluted with EtOAc (50 mL) and washed with 1N 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)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-((S)-3-hydroxypyrrolidine-1-carbonyl)phenoxy)pyrrolidin-2-one (0.0353 g, 0.0678 mmol, 30.6% yield). Mass spectrum (apci) m/z=521.0 (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 preparative HPLC
  7. additionThe combined fractions were diluted with EtOAc (50 mL)
  8. washwashed with 1N 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-45e460a8dcdd45b09543c5fffbb07e7b
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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