Acetic Acid → 7-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-2-oxa-7-azaspiro[3.5]nonane

HRID 1923069Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1923069
[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].FC(F)(F)C(O)=O.[CH2:37]1[C:40]2([CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH2:39][O:38]1.COC(OC)OC.C(O)(=O)C.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:43]4[CH2:44][CH2:45][C:40]5([CH2:37][O:38][CH2:39]5)[CH2:41][CH2:42]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]

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeHCID 670747192-Oxa-7-azaspiro[3.5]nonane 2,2,2-trifluoroacetate

Produkt 1

HCID 596061107-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-2-oxa-7-azaspiro[3.5]nonaneAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.075 g, 0.19 mmol), 2-oxa-7-azaspiro[3.5]nonane trifluoroacetate (0.05 g, 0.20 mmol) in DCE (2 mL), trimethoxymethane (0.204 mL, 1.9 mmol) and acetic acid (0.011 mL, 0.2 mmol) was stirred for 2 h at room temperature. Sodium triacetoxyborohydride (0.061 g, 0.29 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was partitioned between DCM and water, the organic layer was separated, washed with brine, dried over sodium sulphate and concentrated. The residue was purified by flash chromatography (Si—PPC, MEOH:DCM gradient 0:100 to 10:90) to give 324 as a white solid (0.066 g, 70%). LCMS (Method G): RT=5.88 min, [M+H]+ 503.2. 1H NMR (CDCl3, 400 MHz) δ 8.03-7.99 (m, 1 H); 7.83-7.79 (m, 1 H); 7.33-7.29 (m, 2 H); 4.48-4.37 (m, 4 H); 4.34-4.30 (m, 4 H); 3.90-3.84 (m, 7 H); 3.76-3.72 (m, 2 H); 3.40 (d, J=8.3 Hz, 2 H); 2.49-2.44 (m, 4 H); 1.95-1.91 (m, 4 H); 1.48 (t, J=7.5 Hz, 3 H)

Aufarbeitung

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. customThe reaction mixture was partitioned between DCM and water
  3. customthe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (Si—PPC, MEOH:DCM gradient 0:100 to 10:90)

Quellen und Nachweise

ORD-Eintrag
ord-233b2d32c0b145b290567c722eceafa0
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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