Sodium triacetoxyborohydride → HCID 59605676, compound

HRID 1923161Notes

Reaction equation

HRID 1923161 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]([C:34]([N:36]2[CH2:40][CH2:39][C@H:38]([OH:41])[CH2:37]2)=[O:35])[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]([C:34]([N:36]5[CH2:40][CH2:39][C@H:38]([OH:41])[CH2:37]5)=[O:35])[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 59606003HCID 59606003, compound

Product 1

HCID 59605676HCID 59605676, compoundYield 30.9%

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 (75 mg, 0.19 mmol), azetidin-3-yl-((S)-3-hydroxypyrrolidin-1-yl)methanone (65 mg, 0.38 mmol), and 4 Å molecular sieves (250 mg) in 1,2-dichloroethane (2 mL) was stirred at RT for 4 h. Sodium triacetoxyborohydride (81 mg, 0.38 mmol) was added and the resulting reaction mixture was stirred at RT under nitrogen atmosphere for 60 h. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The crude residue was loaded on an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to afford 460 as an off-white solid (32 mg, 30%). LCMS (Method I): RT 2.33 min, [M+H]+ 546. 1H NMR (400 MHz, CDCl3): δ 7.98-7.93 (1h, m), 7.71-7.70 (1 H, m), 7.22 (2 H, s), 4.49 (2 H, s), 4.31 (4 H, s), 3.83-3.81 (8 H, m), 3.52-3.50 (9 H, m), 3.32-3.30 (2 H, m), 2.04-1.88 (3 H, m), 1.40 (3 H, t, J=7.47 Hz)

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at RT under nitrogen atmosphere for 60 h
  3. filtrationThe suspension was filtered through Celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. washThe cartridge was washed with DCM/MeOH
  6. washthe desired product was subsequently eluted
  7. additiona mixture of 2M NH3 in MeOH and DCM
  8. customThe residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-9e1c8a8eda384973a6995742fe9eccf2
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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