Sodium triacetoxyborohydride → 4-(2-((2,2-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)methyl)-5-(2-ethyl-1H-benzo[d]imidazol-1-yl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1923367Notes

Reaction equation

HRID 1923367 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[C:11]3[N:16]=[C:15]([CH:17]=O)[S:14][C:12]=3[N:13]=2)[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[N:4]=1)[CH3:2].[CH3:29][C:30]1([CH3:40])[NH:35][CH2:34][CH2:33][N:32]([CH:36]2[CH2:39][O:38][CH2:37]2)[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:29][C:30]1([CH3:40])[CH2:31][N:32]([CH:36]2[CH2:37][O:38][CH2:39]2)[CH2:33][CH2:34][N:35]1[CH2:17][C:15]1[S:14][C:12]2[N:13]=[C:8]([N:7]3[C:6]4[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=4[N:4]=[C:3]3[CH2:1][CH3:2])[N:9]=[C:10]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[C:11]=2[N:16]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 596058695-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carbaldehydeHCID 674922623,3-Dimethyl-1-(oxetan-3-yl)piperazine

Product 1

HCID 596052774-(2-((2,2-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)methyl)-5-(2-ethyl-1H-benzo[d]imidazol-1-yl)thiazolo[5,4-d]pyrimidin-7-yl)morpholineYield 40%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carbaldehyde (200 mg, 0.51 mmol), 3,3-dimethyl-1-oxetan-3-ylpiperazine (100 mg, 0.65 mmol) and 4 Å powdered molecular sieves (200 mg) in DCE (10 mL) was allowed to stir at r.t. for 1 h before the addition of sodium triacetoxyborohydride (150 mg, 0.71 mmol). The resulting mixture was allowed to stir for 5 h then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-1%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 5-98%) affording 813 (111 mg, 40%). LCMS (method G): RT 6.17 min [M+H]+ 549.3. 1H NMR (CDCl3, 400 MHz): δ 8.01-8.00 (1 H, m), 7.75-7.74 (1 H, m), 7.32-7.22 (2 H, m), 4.67 (2 H, t, J=6.47 Hz), 4.59 (2 H, t, J=6.08 Hz), 4.40 (4 H, brd s), 3.87 (6 H, t, J=4.72 Hz), 3.47-3.46 (1 H, m), 3.34 (2 H, q, J=7.47 Hz), 2.75 (2 H, t, J=4.94 Hz), 2.37 (2 H, brd s), 2.15 (2 H, brd s), 1.43 (3 H, t, J=7.47 Hz), 1.20 (6 H, s)

Workup

  1. washwas washed with MeOH
  2. washthe product eluted with 2M NH3/MeOH
  3. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-1%)

Sources & evidence

ORD record
ord-8a1a576efacb4f90ba395f28977d7701
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…