HCID 10407514, compound → HCID 86695381, compound

HRID 1487435Notes

Reaction equation

HRID 1487435 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][CH:8]([Cl:31])[C:9]([NH:11][C@H:12]([CH2:29][F:30])[C@@H:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]#[N:28])=[CH:25][CH:26]=2)=[CH:17][CH:16]=1)[OH:14])=[O:10]>O1CCCC1>[NH2:28][CH2:27][C:24]1[N:23]=[CH:22][C:21]([C:18]2[CH:17]=[CH:16][C:15]([C@@H:13]([OH:14])[C@H:12]([NH:11][C:9](=[O:10])[CH:8]([Cl:31])[Cl:7])[CH2:29][F:30])=[CH:20][CH:19]=2)=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 10407514HCID 10407514, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 86695381HCID 86695381, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To an ice cold solution of lithium aluminum hydride (0.048 g, 1.33 mmol, 4.0 eq) in tetrahydrofuran (10 mL) to −40° C. is added a solution of 2,2-dichloro-N-((1R,2S)-1-(4-(6-cyanopyridin-3-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)acetamide (0.13 g, 0.34 mmol) in tetrahydrofuran (5 mL) at −40° C. Further lithium aluminum hydride is added (0.012 g, 0.33 mmol) three times and reaction mixture is stirred at −40° C. for 4 hours. The reaction mixture is quenched with saturated aqueous sodium sulphate and stirred for 15 minutes followed by filtration. The filtrate is evaporated in vacuo and the crude material purified by column chromatography on silica gel using methanol/CH2Cl2 and ammonia. To the solution of the crude in CH2Cl2 (5 mL) is added trifluoroacetic acid (0.5 mL) and stirred reaction mixture at room temperature for 15 min. Distilled out solvent under vacuum and washed the residue with diethyl ether, and the residue is dissolved in 10% methanol in CH2Cl2 and evaporated to dryness. Washed with n-pentane and dried under vacuum to get the title compound (20 mg): 1HNMR (400 MHz, CDCl3) δ:4.24-4.25 (m, 2H), 4.28-4.32 (m, 0.5H), 4.40-4.44 (m, 0.5H), 4.56-4.60 (m, 0.5H), 4.68-4.72 (m, 0.5H), 4.92 (bs, 1H), 6.02 (bs, 1H), 6.52 (s, 1H), 7.48 (d, J=8.28 Hz, 2H), 7.57 (d, J=10.8 Hz, 1H), 7.73 (d, J=8.04 Hz, 2H), 8.17 (dd, J1=2.28 Hz, J2=8.08 Hz 1H), 8.28 (bs, 2H), 8.65 (d, J=8.84 Hz, 1H), 8.93 (d, 1H, J=2.2 Hz). m/z (CI) 386 [M+H].

Workup

  1. custom(0.012 g, 0.33 mmol) three times and reaction mixture
  2. customThe reaction mixture is quenched with saturated aqueous sodium sulphate
  3. stirringstirred for 15 minutes
  4. filtrationfollowed by filtration
  5. customThe filtrate is evaporated in vacuo
  6. customthe crude material purified by column chromatography on silica gel
  7. additionTo the solution of the crude in CH2Cl2 (5 mL) is added trifluoroacetic acid (0.5 mL)
  8. stirringstirred
  9. customreaction mixture at room temperature for 15 min
  10. distillationDistilled out solvent under vacuum
  11. washwashed the residue with diethyl ether
  12. dissolutionthe residue is dissolved in 10% methanol in CH2Cl2
  13. customevaporated to dryness
  14. washWashed with n-pentane
  15. customdried under vacuum

Sources & evidence

ORD record
ord-ca9ae378eb4c4ee0839f320d30116758
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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