Sodium triacetoxyborohydride → 1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-N-methyl-N-(tetrahydrofuran-3-yl)piperidin-4-amine

HRID 1923110Notes

Reaction equation

HRID 1923110 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[CH3:30][N:31]([CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)[CH:32]1[CH2:36][CH2:35][O:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:40]4[CH2:39][CH2:38][CH:37]([N:31]([CH3:30])[CH:32]5[CH2:36][CH2:35][O:34][CH2:33]5)[CH2:42][CH2:41]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeHCID 59605994HCID 59605994, compound

Product 1

HCID 596061711-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-N-methyl-N-(tetrahydrofuran-3-yl)piperidin-4-amine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (72 g, 0.19 mmol), methylpiperidin-4-yl(tetrahydrofuran-3-yl)amine (42 mg, 0.23 mmol) and 4 Å powdered molecular sieves (200 mg) in DCE (5 mL) was stirred at room temperature for 6.5 h before the addition of sodium triacetoxyborohydride (81 mg, 0.38 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (x 1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 390 as a cream solid (55 mg, 53%). LCMS (Method G): RT 4.96 min [M+H]+ 546.3. 1H NMR (CDCl3, 400 MHz): δ 8.03-7.99 (m, 1 H); 7.77-7.73 (m, 1 H); 7.29-7.23 (m, 2 H); 4.34 (m, 4 H); 3.96 (m, 1 H); 3.91-3.69 (m, 12 H); 3.45-3.26 (m, 3 H); 2.97 (d, J=11.3 Hz, 2 H); 2.51 (m, 1 H); 2.26 (s, 3 H); 2.16 (t, J=11.3 Hz, 2 H); 2.03 (m, 1 H); 1.89 (m, 2 H); 1.76 (s, 2 H); 1.66 (m, 1 H) and 1.45 (t, J=7.5 Hz, 3 H)

Workup

  1. filtrationthen filtered through celite
  2. washwashing with DCM
  3. washThe organic phase was washed with brine (x 1)
  4. concentrationconcentrated in vacuo
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)
  8. washwas washed with MeOH/DCM
  9. washthe product eluted with 2M NH3/MeOH affording 390 as a cream solid (55 mg, 53%)
  10. customRT 4.96 min [M+H]+ 546.3

Sources & evidence

ORD record
ord-be7450e1c2f041d5b4b976ae1b9a41e4
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…