Sodium triacetoxyborohydride → HCID 59605675, compound

HRID 1923280Notes

Reaction equation

HRID 1923280 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[CH2:38][CH2:37][C@H:36]([F:39])[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[CH2:38][CH2:37][C@H:36]([F:39])[CH2:35]5)[CH2:31]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]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 59605936HCID 59605936, compoundHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 59605675HCID 59605675, compoundYield 63%

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 (0.245 g, 0.627 mmol), (S)-1-azetidin-3-yl-3-fluoropyrrolidine (0.109 g, 0.752 mmol) and 4 Å molecular sieves (0.5 g) in DCE (5 mL). The reaction mixture was stirred for 90 min at room temperature. Sodium triacetoxyborohydride (0.266 g, 1.254 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 20:80) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 586 as an off-white solid (0.204 g, 63%). LCMS (Method I): RT=2.46 min, [M+H]+ 520.2 1H NMR (400 MHz, DMSO-d6): δ 8.03-7.99 (m, 1 H), 7.65-7.61 (m, 1 H), 7.27-7.21 (m, 2 H), 5.19 (dt, J=55.8, 5.4 Hz, 1 H), 4.50-3.95 (m, 4 H), 3.87 (s, 2 H), 3.81-3.72 (m, 7 H), 3.40 (dd, J=7.1, 6.1 Hz, 2 H), 3.26 (q, J=7.4 Hz, 2 H), 3.21-3.12 (m, 1 H), 3.12-3.03 (m, 2 H), 2.79-2.65 (m, 2 H), 2.64-2.51 (m, 1 H), 2.34-2.25 (m, 1 H), 2.15-2.03 (m, 1 H), 1.76-1.95 (m, 1 H), 1.33 (t, J=7.4 Hz, 3 H)

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 20:80)

Sources & evidence

ORD record
ord-f146513f3dc5433eafb95957b95e5858
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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