Sodium triacetoxyborohydride → 4-(5-Chloro-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1922757Notes

Reaction equation

HRID 1922757 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[N:10]=[C:9]([CH:11]=O)[S:8][C:6]=2[N:7]=1.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[N:10]=[C:9]([CH2:11][N:19]3[CH2:22][CH:21]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH2:20]3)[S:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 134019734-(Azetidin-3-yl)morpholineHCID 576854055-Chloro-7-morpholinothiazolo[5,4-d]pyrimidine-2-carbaldehyde

Product 1

HCID 596034604-(5-Chloro-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholineYield 61.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 5-chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine-2-carbaldehyde (3.0 g, 10.54 mmol) and 4-azetidin-3-ylmorpholine (1.8 g, 12.66 mmol) in DCE (200 mL) was stirred at ambient temperature for 2 h. Sodium triacetoxyborohydride (3.5 g, 16.5 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (50 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The eluent was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 99:1 to 98:2 to 95:5) to afford 4-(5-chloro-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine as a cream solid (2.66 g, 61%). LCMS (Method C): RT=2.68 min, [M+H]+ 411.3

Workup

  1. washThe cartridge was then washed with MeOH
  2. washthe desired product was subsequently eluted
  3. customThe eluent was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 99:1 to 98:2 to 95:5)

Sources & evidence

ORD record
ord-741fa4b99602492aa5277e71b23d7814
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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