Triethylamine → HCID 118036871, compound

HRID 1778010Notes

Reaction equation

HRID 1778010 reaction equation
[NH2:1][CH2:2][CH2:3][S:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[CH3:11][O:12][CH:13]([O:26][CH3:27])[C:14]1[C:23]([CH:24]=O)=[CH:22][C:21]2[CH2:20][CH2:19][CH2:18][NH:17][C:16]=2[N:15]=1.CCN(CC)CC.[BH4-].[Na+]>CC(N(C)C)=O.CO>[CH3:27][O:26][CH:13]([O:12][CH3:11])[C:14]1[C:23]([CH2:24][NH:1][CH2:2][CH2:3][S:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:22][C:21]2[CH2:20][CH2:19][CH2:18][NH:17][C:16]=2[N:15]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 4311764Sodium borohydrideHCID 20495621HCID 20495621, compound2×HCID 1180364262-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde2×

Product 1

HCID 118036871HCID 118036871, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

A solution of ethyl 2-((2-aminoethyl)thio)acetate (intermediate 210, 675 mg, 2.87 mmol) in DMA (7.5 ml) and MeOH (7.5 ml) was added to a solution of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 710 mg, 3.01 mmol) and Et3N (0.417 mL, 3.01 mmol) in MeOH (7.5 ml) and the reaction mixture was stirred at room temperature for 3 days. NaBH4 (142 mg, 3.75 mmol) was added portion wise and stirring was continued for 40 min at room temperature. Additional Et3N (500 μL, 3.61 mmol) was added and mixture was stirred for 4 h. Solvents were concentrated and the residue was partitioned between DCM and aqueous citric acid (5%). The aqueous layer was extracted with DCM (3×) and the combined organic layers were washed with aqueous citric acid (5%) (3×). The pH value of the combined water layers was adjusted to 9 using aqueous Na2CO3 and the water phase was back extracted with DCM (3×). The organic layers were combined, dried using Na2SO4, filtered and evaporated to yield the title compound as an orange oil. (UPLC-MS 3) tR 0.61 min; ESI-MS 384.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 7.16 (s, 1H), 6.40-6.36 (m, 1H), 5.08 (s, 1H), 4.12-4.05 (m, 2H), 3.61 (s, 2H), 3.36-3.21 (m, 10H), 2.71-2.61 (m, 6H), 1.80-1.72 (m, 2H), 1.19 (t, 3H

Workup

  1. stirringstirring
  2. waitwas continued for 40 min at room temperature
  3. stirringmixture was stirred for 4 h
  4. concentrationSolvents were concentrated
  5. customthe residue was partitioned between DCM and aqueous citric acid (5%)
  6. extractionThe aqueous layer was extracted with DCM (3×)
  7. washthe combined organic layers were washed with aqueous citric acid (5%) (3×)
  8. extractionthe water phase was back extracted with DCM (3×)
  9. customdried
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-e244e95ca9b747bbabde038c7d34db1f
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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