Aluminium lithium hydride → 2-Aminomethyl-5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

HRID 1191086Notes

Reaction equation

HRID 1191086 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:7]1([CH2:10][NH:11][C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=3)[N:16]=2)[CH2:9][CH2:8]1>C1COCC1>[NH2:24][CH2:23][C:20]1[CH:19]=[CH:18][C:17]([C:15]2[N:16]=[C:12]([NH:11][CH2:10][CH:7]3[CH2:9][CH2:8]3)[S:13][CH:14]=2)=[CH:22][N:21]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 598288995-(2-Cyclopropylmethylamino-thiazol-4-yl)-pyridine-2-carbonitrile

Product 1

HCID 598288662-Aminomethyl-5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridineYield 53.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add lithium aluminum hydride (75 mg, 2.0 mmol) portionwise over 1 minute to a solution of 5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine-2-carbonitrile (340 mg, 1.3 mmol) in THF (20 mL) at room temperature under a nitrogen atmosphere. Stir the mixture for 10 min at room temperature. Quench the mixture successively with water (0.1 mL) and 1N NaOH (0.1 mL). Add sodium sulfate to absorb residual water, filter through Celite®, wash with DCM (30 mL) and concentrate in vacuo. Purify the residue by chromatography on silica gel (12 g) eluting with DCM/2M ammonia in methanol (97:3) to obtain the title compound (180 mg, 52%). MS (ES+) m/z: 261.3 (M+H)+.

Workup

  1. customQuench the mixture successively with water (0.1 mL) and 1N NaOH (0.1 mL)
  2. customAdd sodium sulfate to absorb residual water
  3. filtrationfilter through Celite®
  4. washwash with DCM (30 mL)
  5. concentrationconcentrate in vacuo
  6. customPurify the residue by chromatography on silica gel (12 g)
  7. washeluting with DCM/2M ammonia in methanol (97:3)

Sources & evidence

ORD record
ord-49ebbaf916284a1590bbf7361efe7b7d
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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