Lithium Hydroxide → HCID 58533722, compound

HRID 869828Notes

Reaction equation

HRID 869828 reaction equation
[O:1]([CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=O)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:54][C:55]([CH3:60])([CH3:59])[CH2:56][CH2:57][NH2:58]>C1COCC1.CO.O>[CH3:54][C:55]([CH3:60])([CH3:59])[CH2:56][CH2:57][NH:58][C:13](=[O:15])[C:12]1[CH:17]=[CH:18][C:9]([CH2:8][O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[N:10][CH:11]=1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 197093,3-DimethylbutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54674386HCID 54674386, compound

Product 1

HCID 58533722HCID 58533722, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ester 1.2a (800 mg, 3.29 mmol) in THF (16 ml) and MeOH (4 mL) was added a solution of LiOH (316 mg, 13.2 mmol) in water (4 mL) and stirred at room temperature for 4 h. The reaction was quenched upon addition of 1 N HCl (12 mL) and extracted with EtOAc (2×25 mL). The combined organic extracts were dried over MgSO4 and concentrated under vacuum. The residue was dissolved in DMF (24 mL) and DIPEA (1.22 mL, 6.80 mmol) and HATU (1.29 g, 3.40) added sequentially. The solution was placed into multiple vials and reacted with 3,3-dimethylbutylamine (0.18 mmol) and allowed to stir at rt for 20 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (2×3 mL). The combined organic extracts were dried, concentrated and purified by mass-directed prep reverse-phase HPLC: 1H-NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 8.20 (d, J=8.0 Hz, 1H), 8.04 (s, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.36-7.26 (m, 2H), 7.06-6.97 (m, 3H), 6.24 (s, 1H), 5.30 (s, 2H), 3.58-3.50 (m, 2H), 1.81-1.75 (m, 1H), 1.59-1.49 (m, 2H), 0.99 (d, J=7.0 Hz, 6H); LC-MS (214 nm) >98%, 313.2 [M+H].

Workup

  1. customThe reaction was quenched upon addition of 1 N HCl (12 mL)
  2. extractionextracted with EtOAc (2×25 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated under vacuum
  5. dissolutionThe residue was dissolved in DMF (24 mL)
  6. stirringto stir at rt for 20 h
  7. extractionextracted with EtOAc (2×3 mL)
  8. customThe combined organic extracts were dried
  9. concentrationconcentrated
  10. custompurified by mass-directed prep reverse-phase HPLC

Sources & evidence

ORD record
ord-5eb9042ef4064e31b69bfec5854bfcae
Source dataset
uspto-grants-2015_03
Patent number
US08969389B2

Reaction notes

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