HCID 10407514, compound → HCID 86695381, compound

HRID 1520507Notes

Reaction equation

HRID 1520507 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 methonol/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 using methonol/CH2Cl2 and ammonia

Sources & evidence

ORD record
ord-becdb350d6ec47a2a3e1999bcda2ff6e
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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