Formaldehyde → HCID 86727556, compound

HRID 519160Notes

Reaction equation

HRID 519160 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])[CH:13]3[CH3:23])=[CH:10][C:9]=1[NH:24][C:25]1([CH3:29])[CH2:28][NH:27][CH2:26]1.C=O.[BH3-][C:33]#N.[Na+].O>CO.C(O)(=O)C>[CH3:33][N:27]1[CH2:26][C:25]([NH: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[CH:13]([CH3:23])[C:14](=[O:22])[NH:15][N:16]=2)([CH3:29])[CH2:28]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 867275578-(2-Fluorophenyl)-3,5-dihydro-1-methyl-9-[(3-methyl-3-azetidinyl)amino][1,2,4]triazino[3,4-c][1,4]benzoxazin-2(1H)-one

Product 1

HCID 86727556HCID 86727556, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of 7-(2-fluoro-phenyl)-4-methyl-6-(3-methyl-azetidin-3-ylamino)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.216 g, 0.545 mmol) in MeOH (10 mL) and acetic acid (1 mL) was added paraformaldehyde (0.05 g, 1.635 mmol) followed by NaBH3CN (0.068 g, 1.090 mmol). The mixture was stirred at ambient temperature for 30 min. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (30 mL×3). The combined organic phase was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give the residue, which was purified by chromatography on silica gel (eluting with 50% EtOAc in petroleum ether to 10% methanol in EtOAc) to give 6-(1,3-dimethyl-azetidin-3-ylamino)-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.150 g, 67%). 1H NMR (CDCl3, 400 MHz): δ 7.37 (m, 2H), 7.24 (m, 2H), 6.78 (s, 1H), 6.02 (s, 1H), 4.78 (m, 1H), 4.55 (m, 2H), 3.90 (m, 2H), 3.80 (m, 2H), 2.75 (s, 3H), 1.59 (s, 3H), 1.48 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.715 min.; MS m/z: 410 [M+H]+.

Workup

  1. extractionthe reaction mixture was extracted with EtOAc (30 mL×3)
  2. washThe combined organic phase was washed with brine (10 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto give the residue, which
  7. customwas purified by chromatography on silica gel (eluting with 50% EtOAc in petroleum ether to 10% methanol in EtOAc)

Sources & evidence

ORD record
ord-416700b743c8428eafaa563ca5370b41
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

Loading…