Lithium aluminum hydride → HCID 66749480, compound

HRID 2402001Notes

Reaction equation

HRID 2402001 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([C:12]1[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[S:14][C:13]=1[C:23]1[NH:27][N:26]=[CH:25][CH:24]=1)[N:7]([C:28](OC(C)(C)C)=O)[CH2:6][CH2:5]2.[AlH4-].[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([C:12]1[CH:16]=[C:15]([C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)[S:14][C:13]=1[C:23]1[NH:27][N:26]=[CH:25][CH:24]=1)[N:7]([CH3:28])[CH2:6][CH2:5]2

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 66749936HCID 66749936, compound

Product 1

HCID 66749480HCID 66749480, compoundYield 15.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 6-chloro-1-[2-(1H-pyrazol-5-yl)-5-pyridin-4-yl-3-thienyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate (41 mg, 0.083 mmol) in tetrahydrofuran (3.0 mL, 37 mmol) was added lithium tetrahydroaluminate (0.249 mmol, 0.249 mmol) in THF (2.0 mM) at −78° C. After the addition, the temperature of the reaction was raised to rt for 30 min and then heated at 85° C. for 5 h. The mixture was quenched with water, diluted with methanol, and extracted with ethyl acetate. The organic phase was dried, filtered and evaporated. The residue was loaded onto silica gel and purified by chromatography to afford 6-chloro-2-methyl-1-[2-(1H-pyrazol-5-yl)-5-pyridin-4-yl-3-thienyl]-1,2,3,4-tetrahydroisoquinoline (5.1 mg, 15%). LCMS AA ES+ 407.2, 409.1; 1H NMR (400 MHz, d4-methanol) δ: 8.48 (d, J=5.06 Hz, 2H), 7.89-7.66 (m, 1H), 7.61 (s, 2H), 7.50-7.31 (br, 1H), 7.17 (s, 1H), 7.00 (d, J=7.98 Hz, 1H), 6.87-6.48 (m, 2H), 5.16-4.94 (m, 1H), 3.34 (s, 1H), 3.28-3.10 (m, 2H), 2.94-2.79 (m, 1H), 2.72-2.56 (m, 1H), 2.26 (s, 3H)

Workup

  1. additionAfter the addition
  2. temperatureheated at 85° C. for 5 h
  3. customThe mixture was quenched with water
  4. additiondiluted with methanol
  5. extractionextracted with ethyl acetate
  6. customThe organic phase was dried
  7. filtrationfiltered
  8. customevaporated
  9. custompurified by chromatography

Sources & evidence

ORD record
ord-403510968e55482ea84e9eb28fed1529
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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