Formaldehyde → HCID 86727592, compound

HRID 519181Notes

Reaction equation

HRID 519181 reaction equation
CO.Cl.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:24]=[C:23]2[C:14]([N:15]3[C:20]([CH2:21][O:22]2)=[N:19][NH:18][C:17](=[O:25])[C@H:16]3[CH3:26])=[CH:13][C:12]=1[CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C=O.[BH3-][C:36]#N.[Na+]>C(O)(=O)C>[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:24]=[C:23]2[C:14]([N:15]3[C:20]([CH2:21][O:22]2)=[N:19][NH:18][C:17](=[O:25])[C@H:16]3[CH3:26])=[CH:13][C:12]=1[CH:27]1[CH2:32][CH2:31][N:30]([CH3:36])[CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 86727590HCID 86727590, compound

Product 1

HCID 86727592HCID 86727592, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of MeOH (10 mL) and acetic acid (1 mL) was added (R)-7-(2-fluoro-phenyl)-4-methyl-6-piperidin-4-yl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloride acid (0.300, 0.761 mmol) and paraformaldehyde (0.228 g, 7.61 mmol) and the reaction mixture was stirred at rt for 4 h. Then NaCNBH3 (0.096 g, 1.52 mmol) was added and the reaction mixture was stirred for 30 min. The solvent was removed in vacuo and the residue was purified by prep-TLC (eluting with 10% MeOH in DCM) to give (R)-7-(2-fluoro-phenyl)-4-methyl-6-(1-methyl-piperidin-4-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.160 g, 51%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 7.50-7.41 (m, 1H), 7.32-7.26 (m, 2H), 7.25-7.19 (m, 1H), 7.09 (s, 1H), 6.86 (s, 1H), 5.02-4.93 (m, 1H), 4.70-4.59 (m, 2H), 3.63-3.46 (m, 2H), 3.04-2.89 (m, 2H), 2.84 (s, 3H), 2.76 (m, 1H), 2.28-2.01 (m, 3H), 1.96-1.83 (m, 1H), 1.52 (d, J=6.4 Hz, 3H). LCMS (Table 1, Method 4) Rt=1.617 min; MS m/z: 409 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred for 30 min
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by prep-TLC (eluting with 10% MeOH in DCM)

Sources & evidence

ORD record
ord-497deab7e7db43cc9888bd094082f3bf
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

Loading…