Formaldehyde → HCID 18428688, compound

HRID 1279636Notes

Reaction equation

HRID 1279636 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH3:21])=[C:16]([C:22]([F:25])([F:24])[F:23])[CH:15]=1)[C:7]([NH2:9])=[O:8].C=O.[C:28](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O.N>[CH3:1][N:2]([CH2:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH3:21])=[C:16]([C:22]([F:25])([F:24])[F:23])[CH:15]=1)[C:7]([NH2:9])=[O:8])[CH3:28]

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 18428663HCID 18428663, compound

Product 1

HCID 18428688HCID 18428688, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The amide from example 177 (105 mg, 0.28 mmol) was suspended in DCM (3 mL) and treated with formaldehyde (37% aqueous, 35 μL, 0.425 mmol). The mixture was stirred for 30 minutes (dissolution had occurred by this stage) and then treated with sodium tri(acetoxy)borohydride (120 mg, 0.567 mmol). The reaction was stirred overnight and then diluted with water (5 mL), basified with 880 ammonia (1 mL) and extracted with DCM (3×10 mL). The combined organic extracts were washed with brine (5 mL), dried (MgSO4) and evaporated to a white solid. Purification by flash chromatography [SiO2; DCM, MeOH, 880 NH3 (95:5:0.5)] afforded the title amide as a white powder (85 mg, 78%); Free base: δH (CDCI3, 400 MHz) 2.24 (6 H, s), 2.46 (3 H, s), 3.50 (2 H, s), 5.47-6.15 (2 H, brm), 6.85 (1 H, d), 7.03 (1 H, d), 7.23 (1 H, s), 7.35 (1 H, d), 7.71 (1 H, d), 7.90 (1 H, s); MS m/z (TS+) 385 (MH+)

Workup

  1. dissolutiondissolution
  2. stirringThe reaction was stirred overnight
  3. extractionextracted with DCM (3×10 mL)
  4. washThe combined organic extracts were washed with brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated to a white solid
  7. customPurification by flash chromatography [SiO2; DCM, MeOH, 880 NH3 (95:5:0.5)]

Sources & evidence

ORD record
ord-e59509dc277548169f765c4f74b3bcec
Source dataset
uspto-grants-2002_09
Patent number
US06448293B1

Reaction notes

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