Formaldehyde → HCID 86727615, compound

HRID 519196Notes

Reaction equation

HRID 519196 reaction equation
Cl.[CH3:2][C@@H:3]1[CH2:8][NH:7][C@@H:6]([CH3:9])[CH2:5][N:4]1[C:10]1[CH:11]=[C:12]2[C:21](=[CH:22][C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[F:30])[O:20][CH2:19][C:18]1[N:13]2[C@H:14]([CH3:32])[C:15](=[O:31])[NH:16][N:17]=1.C=O.[BH3-][C:36]#N.[Na+].C([O-])(O)=O.[Na+]>CC(O)=O.CO>[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:23]1[CH:22]=[C:21]2[C:12]([N:13]3[C:18]([CH2:19][O:20]2)=[N:17][NH:16][C:15](=[O:31])[C@H:14]3[CH3:32])=[CH:11][C:10]=1[N:4]1[CH2:5][C@H:6]([CH3:9])[N:7]([CH3:36])[CH2:8][C@H:3]1[CH3:2]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86727612HCID 86727612, compound

Product 1

HCID 86727615HCID 86727615, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of (R)-6-((2R,5S)-2,5-dimethyl-piperazin-1-yl)-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloride (0.040 g, 0.094 mmol) in AcOH (1 mL) and MeOH (10 mL) was added paraformaldehyde (0.028 g, 0.945 mmol) and the reaction mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.015 g, 0.236 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. Aqueous saturated NaHCO3 solution (10 mL) was added and the reaction mixture was extracted with EtOAc (3×20 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc) to give (R)-7-(2-fluoro-phenyl)-4-methyl-6-((2R,5S)-2,4,5-trimethyl-piperazin-1-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.011 g, 60%). 1H NMR (400 MHz, CD3OD): δ 7.33-7.41 (m, 1H), 7.18-7.29 (m, 2H), 7.14 (m, 1H), 7.06 (s, 1H), 6.93 (s, 1H), 4.58-4.69 (m, 3H), 3.18 (m, 2H), 2.96 (m, 1H), 2.71 (m, 2H), 2.59 (m, 3H), 2.27 (m, 1H), 1.48 (d, J=6.5 Hz, 3H), 1.15 (d, J=4.8 Hz, 3H), 0.75 (d, J=6.0 Hz, 3H). LC/MS (Table 1, Method 4) Rt=1.708 min.; MS m/z: 439 [M+H]+. SFC (Table 1, Method 56), Rt=2.337 min.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature overnight
  2. extractionthe reaction mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-f809ee688b634aa9bf5a12a5a1711c0f
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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