Formaldehyde → HCID 71622816, compound

HRID 1479060Notes

Reaction equation

HRID 1479060 reaction equation
[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH:24]4[CH2:28][CH2:27][NH:26][CH2:25]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:29].C=O.[BH4-].[Na+].[C:34](O)(C(F)(F)F)=O>C1COCC1.CC(=O)OCC>[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH:24]4[CH2:28][CH2:27][N:26]([CH3:34])[CH2:25]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:29]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 71610205HCID 71610205, compound

Product 1

HCID 71622816HCID 71622816, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Example 68 (150 mg; 0.36 mmol; 1 eq.), formaldehyde (0.27 mL; 3.64 mmol; 10 eq.) and NaBH4 (69 mg; 1.82 mmol; 5 eq.) in THF (12 mL) was cooled to 0° C. and TFA (1 mL) was added. The reaction mixture was stirred at room temperature for 18 hours then diluted with EA. The organic phase was washed with 0.1M NaOH (2×), dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM/MeOH/TEA) afforded the title compound (75 mg, 48%) as white foam. 1H NMR (DMSO-d6) δ 7.47-7.38 (m, 1H), 7.33-7.25 (m, 1H), 7.09-6.99 (m, 2H), 4.99-4.89 (m, 1H), 4.82 (m, 2H), 4.65-4.42 (m, 2H), 2.88-2.75 (m, 4H), 2.62 (s, 1.5H), 2.60-2.52 (m, 2.5H), 2.37-2.20 (m, 2H), 2.19 (s, 1.5H), 2.18 (s, 1.5H), 1.80-1.66 (m, 1H), 1.46-1.31 (m, 1H). HPLC (max plot) 95.6%, Rt 2.63 min. UPLC/MS: (MS+) 426.5 ([M+H]+).

Workup

  1. washThe organic phase was washed with 0.1M NaOH (2×)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by column chromatography (DCM/MeOH/TEA)

Sources & evidence

ORD record
ord-85cb754d7bf04965b0f2129df1d27fdb
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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