Triethylamine → 7-(Dimethoxymethyl)-6-(1-(oxetan-3-yl)piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine

HRID 1778068Notes

Reaction equation

HRID 1778068 reaction equation
Cl.[CH3:2][O:3][CH:4]([O:21][CH3:22])[C:5]1[N:14]=[C:13]2[C:8]([CH2:9][CH2:10][CH2:11][NH:12]2)=[CH:7][C:6]=1[CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.CCN(CC)CC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O>[CH3:22][O:21][CH:4]([O:3][CH3:2])[C:5]1[N:14]=[C:13]2[C:8]([CH2:9][CH2:10][CH2:11][NH:12]2)=[CH:7][C:6]=1[CH:15]1[CH2:16][CH2:17][N:18]([CH:25]2[CH2:26][O:23][CH2:24]2)[CH2:19][CH2:20]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 1180364207-(Dimethoxymethyl)-6-(piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine hydrochloride2×

Product 1

HCID 1180365997-(Dimethoxymethyl)-6-(1-(oxetan-3-yl)piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 7-(dimethoxymethyl)-6-(piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine hydrochloride (Intermediate 342, 0.94 g, 2.294 mmol), 3-oxetanone (0.777 g, 10.78 mmol) and Et3N (0.96 ml, 6.88 mmol) in 1,2-dichloroethane (50 ml) was cooled to 0° C., treated with sodium triacetoxyborohydride (1.54 g, 6.88 mmol) and then slowly warmed to room temperature. After 1.5 h, the reaction mixture was poured into H2O and evaporated to dryness. The crude material was purified by reverse phase chromatography (Reprosil C18/250×30 mm/5 um, 0.1% TFA in H2O/acetonitrile 70:30 to 5:95). The product-containing fractions were treated with NaHCO3 and then concentrated to dryness. The residue was suspended in MeOH, stirred for 1 h and filtered, washing with additional MeOH. The filtrate was evaporated to give the title compound as a yellow solid. (UPLC-MS 3) tR 0.34 min; ESI-MS 348.2 [M+H]+.

Workup

  1. temperatureslowly warmed to room temperature
  2. customevaporated to dryness
  3. customThe crude material was purified by reverse phase chromatography (Reprosil C18/250×30 mm/5 um, 0.1% TFA in H2O/acetonitrile 70:30 to 5:95)
  4. additionThe product-containing fractions were treated with NaHCO3
  5. concentrationconcentrated to dryness
  6. filtrationfiltered
  7. washwashing with additional MeOH
  8. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-5fb5ac45e5d8421aa14dbfbd9c455f21
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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