Formaldehyde → HCID 86727508, compound

HRID 519123Notes

Reaction equation

HRID 519123 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:21]=[C:20]2[C:11]([N:12]3[C:17]([CH2:18][O:19]2)=[N:16][NH:15][C:14](=[O:22])[C@H:13]3[CH3:23])=[CH:10][C:9]=1[C@H:24]([C:26]1([CH3:30])[CH2:29][NH:28][CH2:27]1)[CH3:25].C=O.[BH3-][C:34]#N.[Na+].C([O-])(O)=O.[Na+]>CC(O)=O.CO>[CH3:34][N:28]1[CH2:29][C:26]([C@@H:24]([C:9]2[CH:10]=[C:11]3[C:20](=[CH:21][C:8]=2[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[O:19][CH2:18][C:17]2[N:12]3[C@H:13]([CH3:23])[C:14](=[O:22])[NH:15][N:16]=2)[CH3:25])([CH3:30])[CH2:27]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86727507HCID 86727507, compound

Product 1

HCID 86727508HCID 86727508, compoundYield 41.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of (R)-7-(2-fluoro-phenyl)-4-methyl-6-[(R)-1-(3-methyl-azetidin-3-yl)-ethyl]-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.04 g, 0.098 mmol) in AcOH (0.5 mL) and MeOH (5 mL) was added paraformaldehyde (0.029 g, 0.979 mmol) and the resulting mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.015 g, 0.245 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. Aqueous NaHCO3 (10 mL) was added and the aqueous solution was extracted with EtOAc (3×30 mL). The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo and the residue was purified by prep-HPLC (Table 3, Method 25) to give (R)-6-[(R)-1-(1,3-dimethyl-azetidin-3-yl)-ethyl]-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.017 g, 40%). 1H NMR (CD3OD, 400 MHz): δ 7.40-7.48 (m, 1H), 7.15-7.32 (m, 3H), 6.91 (s, 1H), 6.84 (s, 1H), 4.83 (m, 1H), 4.58-4.69 (m, 2H), 2.87-3.19 (m, 3H), 2.73-2.87 (m, 2H), 2.10-2.22 (m, 3H), 1.50 (m, 3H), 1.25-1.35 (m, 3H), 1.13-1.23 (m, 3H). LC/MS (Table 1, Method 4) Rt=1.858 min; MS m/z: 423 [M+H]+. SFC (Table 1, Method 15) Rt=1.592 min.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature overnight
  2. extractionthe aqueous solution was extracted with EtOAc (3×30 mL)
  3. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThe filtrate was evaporated in vacuo
  6. customthe residue was purified by prep-HPLC (Table 3, Method 25)

Sources & evidence

ORD record
ord-2981c556054b4745b7a2574ba0def394
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

Loading…