Aluminium lithium hydride → (4-methyl-2-(1H-pyrazolo[3,4-b]pyridin-4-yl)-4,5,6,7-tetrahydrobenzo[d]thiazol-4-yl)methanamine

HRID 44678Notes

Reaction equation

HRID 44678 reaction equation
[CH3:1][C:2]1([C:20]#[N:21])[C:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]4[NH:17][N:18]=[CH:19][C:12]=34)[S:10][C:6]=2[CH2:5][CH2:4][CH2:3]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:1][C:2]1([CH2:20][NH2:21])[C:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]4[NH:17][N:18]=[CH:19][C:12]=34)[S:10][C:6]=2[CH2:5][CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66645490HCID 66645490, compound

Product 1

HCID 49800491(4-methyl-2-(1H-pyrazolo[3,4-b]pyridin-4-yl)-4,5,6,7-tetrahydrobenzo[d]thiazol-4-yl)methanamineYield 4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-methyl-2-(1H-pyrazolo[3,4-b]pyridin-4-yl)-6,7-dihydro-5H-1,3-benzothiazole-4-carbonitrile (67 mg, 0.2268 mmol) in THF (7 mL) was allowed to cool in an ice bath and treated with LiAlH4 in THF (453.6 μL of 2 M, 0.9072 mmol) dropwise. The mixture was allowed to warm to RT, stirred for 3 hours and then quenched with water whilst cooling. The aqueous layer was extracted with EtOAc (2×) and the combined organics dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (2.7 mg, 4% Yield). 1H NMR (DMSO, 400 MHz) δ 1.29 (3H, s), 1.50-1.55 (1H, m), 1.85-1.98 (3H, m), 2.77-2.93 (4H, m), 7.58 (1H, d), 8.58 (1H, s), 8.60 (1H, d); MS (ES+) 300.05

Workup

  1. temperatureto cool in an ice bath
  2. customquenched with water
  3. temperaturewhilst cooling
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialthe combined organics dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-d68e04b3c4334c0e8292600e10de1010
Source dataset
uspto-grants-2013_09
Patent number
US08541445B2

Reaction notes

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