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

HRID 1923270Notes

Reaction equation

HRID 1923270 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].[F:30][C:31]1([F:41])[CH2:34][N:33]([CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:41][C:31]1([F:30])[CH2:34][N:33]([CH:35]2[CH2:36][CH2:37][N:38]([CH2:18][C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)[CH2:39][CH2:40]2)[CH2:32]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 596056804-(3,3-Difluoroazetidin-1-yl)piperidineHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596054264-(8-((4-(3,3-difluoroazetidin-1-yl)piperidin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholineYield 53%

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 (0.139 g, 0.36 mmol), 4-(3,3-difluoroazetidin-1-yl)piperidine (0.075 g, 0.43 mmol) and 4 Å molecular sieves (0.4 g) in DCE (5 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.15 g, 0.71 mmol) was added and the reaction mixture was stirred for 72 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 12:88) 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 576 as an off-white solid (0.104 g, 53%). LCMS (Method I): RT=2.61 min, [M+H]+ 552.2 1H NMR (400 MHz, DMSO-d6): δ 8.03-7.99 (m, 1 H), 7.65-7.61 (m, 1 H), 7.27-7.20 (m, 2 H), 4.60-3.95 (s, 4 H), 3.81 (s, 3 H), 3.80-3.74 (m, 6 H), 3.52 (t, J=12.3 Hz, 4 H), 3.27 (q, J=7.4 Hz, 2 H), 2.79-2.70 (m, 2 H), 2.20-2.10 (m, 3 H), 1.68-1.59 (m, 2 H), 1.34 (t, J=7.4 Hz, 3 H), 1.30-1.17 (m, 2 H)

Workup

  1. stirringthe reaction mixture was stirred for 72 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 12:88)

Sources & evidence

ORD record
ord-23b148283b0541649fd83c8899c24794
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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