Formaldehyde → HCID 76285725, compound

HRID 519064Notes

Reaction equation

HRID 519064 reaction equation
[CH3:1][CH:2]1[N:15]2[C:6]([CH2:7][O:8][C:9]3[C:14]2=[CH:13][C:12]([NH:16][C:17]2([CH3:21])[CH2:20][NH:19][CH2:18]2)=[C:11]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:10]=3)=[N:5][NH:4][C:3]1=[O:28].C=O.[BH3-][C:32]#N.[Na+]>CO.CC(O)=O>[CH3:32][N:19]1[CH2:20][C:17]([NH:16][C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][C:11]=2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[O:8][CH2:7][C:6]2[N:15]3[CH:2]([CH3:1])[C:3](=[O:28])[NH:4][N:5]=2)([CH3:21])[CH2:18]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 76287822HCID 76287822, compound

Product 1

HCID 76285725HCID 76285725, compoundYield 102.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-methyl-6-(3-methyl-azetidin-3-ylamino)-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.095 g, 57% purity, 0.15 mmol) and paraformaldehyde (0.015 g, 0.45 mmol) in MeOH (10 mL) and AcOH (1 mL) was heated at 80° C. for 2 h. NaBH3CN (0.019 g, 0.30 mmol) was added and the reaction mixture was stirred at 80° C. for 0.5 h. The reaction mixture was cooled to ambient temperature. The solvent was removed in vacuo and the residue was washed with aqueous saturated Na2CO3 solution (2 mL). The aqueous phase was extracted with EtOAc (4×20 mL). The combined organic layer was dried, filtered and concentrated in vacuo to give crude 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.060 g, 78% over two steps), which was used in the next step directly. LC/MS (Table 1, Method 2) Rt=0.924 min; MS m/z: 392 [M+H]+. A solution of 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.060 g, 0.15 mmol) in ammonium hydroxide (25%, 5 mL) and dioxane (5 mL) was stirred at ambient temperature for 2 h. The solvent was removed in vacuo and the residue was purified by preparative HPLC (Table 3, Method 16) to give 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one trifluoroacetic acid (0.022 g, 27%). LC/MS (Table 1, Method 4) Rt=1.722 min; MS m/z: 392 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customThe solvent was removed in vacuo
  3. washthe residue was washed with aqueous saturated Na2CO3 solution (2 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (4×20 mL)
  5. customThe combined organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c6ea5ada0978402c9a66b11d942eb157
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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