Formaldehyde → HCID 86727607, compound

HRID 519191Notes

Reaction equation

HRID 519191 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]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:23])[C@H:14]3[CH3:24])=[CH:11][C:10]=1[C@@H:25]1[CH2:30][CH2:29][NH:28][CH2:27][C@@H:26]1[CH3:31].C=O.[BH3-][C:35]#N.[Na+].C([O-])(O)=O.[Na+]>CC(O)=O.CO>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]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:23])[C@H:14]3[CH3:24])=[CH:11][C:10]=1[C@@H:25]1[CH2:30][CH2:29][N:28]([CH3:35])[CH2:27][C@@H:26]1[CH3:31]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86727606HCID 86727606, compound

Product 1

HCID 86727607HCID 86727607, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a mixture of (R)-7-(2,6-difluoro-phenyl)-4-methyl-6-((3R,4R)-3-methyl-piperidin-4-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.005 g, 0.012 mmol) in AcOH (0.2 mL) and MeOH (2 mL) was added paraformaldehyde (0.004 g, 0.117 mmol) and the reaction mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.002 g, 0.029 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. Aqueous saturated NaHCO3 solution (30 mL) was added and the reaction mixture was extracted with EtOAc (3×50 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc) to give (R)-7-(2,6-difluoro-phenyl)-6-((3R,4R)-1,3-dimethyl-piperidin-4-yl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.0041 g, 79%). 1H NMR (400 MHz, CD3OD): 7.47-7.54 (m, 1H), 7.13 (t, J=7.91 Hz, 2H), 6.96 (s, 1H), 6.89 (s, 1H), 4.94-4.96 (m, 1H), 4.67 (m, 2H), 3.58 (m, 1H), 2.89-3.11 (m, 3H), 2.82 (s, 3H), 2.44-2.60 (m, 2H), 2.26-2.42 (m, 1H), 1.94 (m, 2H), 1.51 (d, J=6.4 Hz, 3H), 0.94 (d, J=7.4 Hz, 3H). LC/MS (Table 1, Method 4) Rt=1.656 min.; MS m/z: 441 [M+H]+. SFC (Table 2, Method 28), Rt=4.708 min.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature overnight
  2. extractionthe reaction mixture was extracted with EtOAc (3×50 mL)
  3. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-4f3173e6bceb4cffadcb30918ae4a315
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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