Sodium triacetoxyborohydride → 4-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)-2,2-dimethylmorpholine

HRID 1923076Notes

Reaction equation

HRID 1923076 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].[NH:30]1[CH2:33][CH:32]([N:34]2[CH2:39][CH2:38][O:37][C:36]([CH3:41])([CH3:40])[CH2:35]2)[CH2:31]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:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][O:37][C:36]([CH3:41])([CH3:40])[CH2:35]5)[CH2:31]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 627847954-(Azetidin-3-yl)-2,2-dimethylmorpholine

Product 1

HCID 596060864-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)-2,2-dimethylmorpholine

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 (112 mg, 0.29 mmol), 4-azetidin-3-yl-2,2-dimethylmorpholine (58 mg, 0.34 mmol) and 4 Å powdered molecular sieves (200 mg) in DCE (5 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (121 mg, 0.57 mmol). The reaction mixture was stirred for 40 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 331 as a yellow solid (121 mg, 76%). LCMS (Method G): RT 6.85 min [M+H]+ 546.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.77-7.73 (m, 1 H); 7.29-7.22 (m, 2 H); 4.35 (m, 4 H); 3.91-3.82 (m, 9 H); 3.73 (m, 2 H); 3.57 (t, J=6.6 Hz, 2 H); 3.35 (q, J=7.5 Hz, 2 H); 3.10 (t, J=6.6 Hz, 2 H); 2.98 (p, J=6.6 Hz, 1 H); 2.24 (m, 2 H); 2.04 (s, 2 H); 1.44 (t, J=7.5 Hz, 3 H) and 1.25 (s, 6 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 331 as a yellow solid (121 mg, 76%)
  10. customRT 6.85 min [M+H]+ 546.3

Sources & evidence

ORD record
ord-59c662713d534cc08c0f18d03c33b804
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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