Lithium borohydride → HCID 178434534, compound

HRID 1049152Notes

Reaction equation

HRID 1049152 reaction equation
[C:1]([CH2:3][C:4]1([N:25]2[CH:29]=[C:28]([C:30]3[C:31]([CH3:35])=[N:32][NH:33][CH:34]=3)[C:27]([C:36](OCC)=[O:37])=[N:26]2)[CH2:7][N:6]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([C:15]([NH:17][C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])=[O:16])=[CH:10][C:9]=2[F:24])[CH2:5]1)#[N:2].[BH4-].[Li+]>C1COCC1>[C:1]([CH2:3][C:4]1([N:25]2[CH:29]=[C:28]([C:30]3[C:31]([CH3:35])=[N:32][NH:33][CH:34]=3)[C:27]([CH2:36][OH:37])=[N:26]2)[CH2:7][N:6]([C:8]2[C:9]([F:24])=[CH:10][C:11]([C:15]([NH:17][C@@H:18]([CH3:23])[C:19]([F:21])([F:22])[F:20])=[O:16])=[C:12]([F:14])[CH:13]=2)[CH2:5]1)#[N:2]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 178470456HCID 178470456, compound

Product 1

HCID 178434534HCID 178434534, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 1-{3-(cyanomethyl)-1-[2,5-difluoro-4-({[(1S)-2,2,2-trifluoro-1-methylethyl]amino}carbonyl)phenyl]azetidin-3-yl}-3′-methyl-1H,1′H-4,4′-bipyrazole-3-carboxylate (35 mg, 0.062 mmol) in THF (0.5 mL) was added 2.0 M lithium tetrahydroborate in THF (0.12 mL, 0.25 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water slowly. The aqueous layer was extracted with ethyl acetate. The organic layer was concentrated. The resulting residue was purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product. 1H NMR (400 MHz, CDCl3) δ 7.79-7.68 (m, 2H), 7.61 (s, 1H), 6.65 (m, 1H), 6.20 (m, 1H), 4.99-4.89 (m, 1H), 4.68 (s, 2H), 4.60 (d, J=8.5 Hz, 2H), 4.45 (dd, J=8.9 and 2.0 Hz, 2H), 3.38 (s, 2H), 2.34 (s, 3H), 1.41 (d, J=7.0 Hz, 3H). LCMS calculated for C23H23F5N7O2 (M+H)+: m/z=524.2. Found: 524.0.

Workup

  1. customThe reaction was quenched with water slowly
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. customThe resulting residue was purified with prep-LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-862919266b26409c81c8f372be90f6cc
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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