Formaldehyde → HCID 71610224, compound

HRID 1479071Notes

Reaction equation

HRID 1479071 reaction equation
[C:1](O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:17]([CH3:18])=[N:16][C:15]2[N:11]([N:12]=[C:13]3[CH2:21][N:20]([C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=4[O:31][C@@H:32]4[CH2:36][CH2:35][NH:34][CH2:33]4)=[O:23])[CH2:19][C:14]3=2)[C:10]=1[CH3:37].C=O.[BH4-].[Na+]>C1COCC1.CC(=O)OCC>[Cl:8][C:9]1[C:17]([CH3:18])=[N:16][C:15]2[N:11]([N:12]=[C:13]3[CH2:21][N:20]([C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=4[O:31][C@@H:32]4[CH2:36][CH2:35][N:34]([CH3:1])[CH2:33]4)=[O:23])[CH2:19][C:14]3=2)[C:10]=1[CH3:37]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 71610220HCID 71610220, compound

Product 1

HCID 71610224HCID 71610224, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

TFA (15 μL) was added to a cold (0° C.) mixture of Example 80 (150 mg; 0.35 mmol; 1 eq.), formaldehyde (0.26 mL; 3.49 mmol; 10 eq.) and NaBH4 (66 mg; 1.74 mmol; 5 eq.) in THF (12 mL) and the resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with EA, washed with 0.1M NaOH, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (EA to EA/MeOH/TEA, 90/10/2) afforded the title compound (50 mg, 32%) as yellow foam. 1H NMR (DMSO-d6) δ 7.39-7.30 (m, 1H), 6.98 (dd, J=11.5, 2.3 Hz, 1H), 6.87 (td, J=8.4, 2.3 Hz, 1H), 5.01-4.92 (m, 1H), 4.85-4.78 (m, 2H), 4.66-4.45 (m, 2H), 2.85 (s, 1.5H), 2.81 (s, 1.5H), 2.79-2.70 (m, 1H), 2.62 (s, 1.5H), 2.60-2.52 (m, 2H), 2.55 (s, 1.5H), 2.35-2.2.20 (m, 2H), 2.17 (s, 1.5H), 2.16 (s, 1.5H), 1.81-1.60 (m, 1H). HPLC (max plot) 96.7%, Rt 2.74 min. UPLC/MS: (MS+) 444.5 ([M+H]+).

Workup

  1. washwashed with 0.1M NaOH
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by column chromatography (EA to EA/MeOH/TEA, 90/10/2)

Sources & evidence

ORD record
ord-dea92030ecbd4fb7846058021bb8bc10
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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