HCID 10407514, compound → HCID 86695381, compound

HRID 1487508Notes

Reaction equation

HRID 1487508 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 32.7%

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 afford title compound (43 mg): 1H NMR (400 MHz, CDCl3) δ: 4.20-4.24 (m, 2H), 4.27-4.29 (m, 0.5H), 4.39-4.43 (m, 0.5H), 4.56-4.59 (m, 1H), 4.67-4.69 (m, 0.5H), 4.89-4.90 (m, 1H), 5.99 (d, J=4.2 Hz, 1H), 6.52 (s, 1H), 7.46-7.48 (m, 3H), 7.64-7.69 (m, 3H), 8.06-8.10 (m, 1H), 8.63 (d, J=8.76 Hz, 1H). LC-MS (m/z): [M+H]=386.10.

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

Sources & evidence

ORD record
ord-831b7dedc825432c8ec76a5bd37f5ea8
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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