Sodium triacetoxyborohydride → 1-isopropyl-4-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-one

HRID 1923252Notes

Reaction equation

HRID 1923252 reaction equation
[CH:1]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]=O)[N:15]3[CH3:18])=[C:11]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:10]=2)[C:7]2[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=2[N:5]=1)([CH3:3])[CH3:2].[CH:31]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][C:35]1=[O:40])([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:31]([N:34]1[CH2:39][CH2:38][N:37]([CH2:19][C:14]2[N:15]([CH3:18])[C:16]3[C:12]([N:13]=2)=[C:11]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[N:10]=[C:9]([N:8]2[C:7]4[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=4[N:5]=[C:4]2[CH:1]([CH3:2])[CH3:3])[N:17]=3)[CH2:36][C:35]1=[O:40])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 150574011-(Propan-2-yl)piperazin-2-oneHCID 866482702-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596056821-isopropyl-4-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-oneYield 85.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.15 g, 0.37 mmol), 1-isopropylpiperazin-2-one (0.078 g, 0.44 mmol) and 4 Å molecular sieves (0.372 g) in DCE (3 mL) was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.157 g, 0.74 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc, gradient 0:100 to 10:90) to give 555 as an off-white solid (0.168 g, 84%). LCMS (Method I): RT=3.43 min, [M+H]+ 532.3. 1H NMR (400 MHz, DMSO-d): δ 7.93-7.89 (m, 1 H); 7.68-7.63 (m, 1 H); 7.28-7.23 (m, 2 H); 4.64-4.58 (m, 1 H); 4.29-4.21 (m, 4 H); 3.97-3.90 (m, 1 H); 3.90 (d, J=4.6 Hz, 2 H); 3.80 (s, 3 H); 3.78 (t, J=4.6 Hz, 4 H); 3.21-3.15 (m, 4 H); 2.78-2.75 (m, 2 H); 1.36 (d, J=6.8 Hz, 6 H); 1.05 (d, J=6.8 Hz, 6 H)

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe reaction mixture was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-ac1f2ddb85a141568c2adb0c12497530
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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