Formaldehyde → HCID 118235640, compound

HRID 627003Notes

Reaction equation

HRID 627003 reaction equation
[CH:1]([OH:3])=[O:2].[F:4][CH:5]([F:36])[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C:14]1[N:18]2[CH:19]=[C:20]([C:24]3[CH:25]=[N:26][C:27]([C:30]4([OH:34])[CH2:33][NH:32][CH2:31]4)=[N:28][CH:29]=3)[C:21]([F:23])=[CH:22][C:17]2=[N:16][C:15]=1[CH3:35].C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)C.C(O)(=O)C>[CH:1]([OH:3])=[O:2].[F:36][CH:5]([F:4])[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C:14]1[N:18]2[CH:19]=[C:20]([C:24]3[CH:25]=[N:26][C:27]([C:30]4([OH:34])[CH2:33][N:32]([CH3:39])[CH2:31]4)=[N:28][CH:29]=3)[C:21]([F:23])=[CH:22][C:17]2=[N:16][C:15]=1[CH3:35]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 118235654HCID 118235654, compound

Product 1

HCID 118235640HCID 118235640, compoundYield 17.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

To a suspension of Example 325 (81%, 195 mg, 0.3 mmol) in ethanol (4 mL) was added 37% aqueous formaldehyde solution (0.1 mL, 1.33 mmol) and the resulting solution was stirred at room temperature for 20 minutes. Sodium triacetoxyborohydride (160 mg, 0.76 mmol) was added in one portion, followed by acetic acid (0.1 mL), and the whole mixture was stirred at room temperature under nitrogen for 2 h. The reaction mixture was diluted and neutralised with saturated sodium bicarbonate solution (15 mL). The crude material was then extracted into dichloromethane (2×20 mL). The combined organic extracts were dried over sodium sulphate, filtered and concentrated under vacuum. The resulting brown oil (140 mg) was purified by preparative HPLC (Method A) to afford the title compound (27 mg, 17%) as a colourless solid. δH (500 MHz, CD3OD) 9.05 (d, J 1.4 Hz, 2H), 8.38-8.35 (m, 2H), 7.41 (d, J 10.9 Hz, 1H), 7.33-7.27 (m, 1H), 7.18 (d, J 7.9 Hz, 1H), 7.14 (td, J 7.6, 0.9 Hz, 1H), 7.10 (dd, J 7.6, 1.7 Hz, 1H), 6.91 (t, J 74.0 Hz, 1H), 4.72 (d, J 11.3 Hz, 2H), 4.42 (s, 2H), 4.35 (d, J 11.4 Hz, 2H), 3.08 (s, 3H), 2.42 (s, 3H). Method D HPLC-MS: MH+ m/z 470, RT 1.09 minutes.

Workup

  1. stirringthe whole mixture was stirred at room temperature under nitrogen for 2 h
  2. additionThe reaction mixture was diluted
  3. extractionThe crude material was then extracted into dichloromethane (2×20 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe resulting brown oil (140 mg) was purified by preparative HPLC (Method A)

Sources & evidence

ORD record
ord-1e54a5157b664840832b9ed16121402c
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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