Formaldehyde → HCID 71610208, compound

HRID 1479059Notes

Reaction equation

HRID 1479059 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][C:20]([F:23])=[CH:19][C:18]=4[O:24][CH:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:31].C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[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][C:20]([F:23])=[CH:19][C:18]=4[O:24][CH:25]4[CH2:30][CH2:29][N:28]([CH3:34])[CH2:27][CH2:26]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:31]

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 71610191HCID 71610191, compound

Product 1

HCID 71610208HCID 71610208, compoundYield 35.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of Example 64 (100 mg; 0.21 mmol; 1 eq.), paraformaldehyde (56 mg; 0.62 mmol; 3 eq.) and sodium triacetoxyborohydride (88 mg; 0.42 mmol; 2 eq.) in DCE (7 mL) was stirred at reflux for 16 hours. Paraformaldehyde (56 mg; 0.62 mmol; 3 eq.) and sodium triacetoxyborohydride (88 mg; 0.42 mmol; 2 eq.) were added and the reaction mixture was stirred at reflux for one hour. The mixture was partitioned between EA and 1M NaOH and the aqueous layer extracted with EA. The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (2% to 5% MeOH in DCM) followed by recrystallization from ACN afforded the title compound (34 mg, 35%) as a white powder. 1H NMR (DMSO-d6) δ 7.44-7.25 (m, 1H), 7.13 (d, J=11.4 Hz, 1H), 6.86 (td, J=8.3, 2.0 Hz, 1H), 4.92-4.69 (m, 2H), 4.69-4.37 (m, 3H), 2.93-2.70 (m, 3H), 2.61 (s, 1.5H), 2.55 (s, 1.5H), 2.42-2.23 (m, 2H), 2.23 2.04 (m, 2H), 2.04-1.93 (m, 3H), 1.91-1.73 (m, 2H), 1.64-1.47 (m, 2H). HPLC (max plot) 97.4%, Rt 2.81 min. UPLC/MS: (MS+) 458.5 ([M+H]+).

Workup

  1. temperatureat reflux for 16 hours
  2. temperatureat reflux for one hour
  3. customThe mixture was partitioned between EA and 1M NaOH
  4. extractionthe aqueous layer extracted with EA
  5. dry with materialThe combined organic phase was dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography (2% to 5% MeOH in DCM)
  8. customfollowed by recrystallization from ACN

Sources & evidence

ORD record
ord-d281e5b3f83a409ab1e74cfa3b9e799c
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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