Formaldehyde → HCID 86727503, compound

HRID 519119Notes

Reaction equation

HRID 519119 reaction equation
Cl.[CH:2]([C:5]1[CH:18]=[C:17]2[C:8]([N:9]3[C:14]([CH2:15][O:16]2)=[N:13][NH:12][C:11](=[O:19])[C@H:10]3[CH3:20])=[CH:7][C:6]=1[C@H:21]([C:23]1([CH3:27])[CH2:26][NH:25][CH2:24]1)[CH3:22])([CH3:4])[CH3:3].C=O.[BH3-][C:31]#N.[Na+]>CO.C(O)(=O)C>[CH3:31][N:25]1[CH2:24][C:23]([C@@H:21]([C:6]2[CH:7]=[C:8]3[C:17](=[CH:18][C:5]=2[CH:2]([CH3:3])[CH3:4])[O:16][CH2:15][C:14]2[N:9]3[C@H:10]([CH3:20])[C:11](=[O:19])[NH:12][N:13]=2)[CH3:22])([CH3:27])[CH2:26]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86727501HCID 86727501, compound

Product 1

HCID 86727503HCID 86727503, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of (R)-7-isopropyl-4-methyl-6-[(R)-1-(3-methyl-azetidin-3-yl)-ethyl]-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloric acid (Example #133, Step G, 0.0227 g, 0.064 mmol) in MeOH (2 mL) and acetic acid (0.2 mL) was added paraformaldehyde (0.765 mL, 0.255 mmol) and the reaction mixture was stirred at ambient temperature for 0.5 h. NaBH3CN (0.008 g, 0.127 mmol) was added and the reaction mixture was stirred at ambient temperature for 0.5 h. The reaction mixture was concentrated in vacuo and the residue was purified by prep-TLC (eluting with 10% MeOH in dichloromethane) to give (R)-6-[(R)-1-(1,3-dimethyl-azetidin-3-yl)-ethyl]-7-isopropyl-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.0199 g, 84%) as a solid. 1H NMR (CD3OD-d4, 400 MHz): δ 7.00 (s, 1H), 6.79 (s, 1H), 4.83 (br. s., 1H), 4.60 (s, 2H), 3.96 (m, 1H), 3.91 (m, 1H), 3.76 (d, J=9.8 Hz, 1H), 3.67 (d, J=9.8 Hz, 1H), 3.38 (m, 1H), 3.18 (m, 1H), 2.71 (s, 3H), 1.48-1.43 (m, 6H), 1.38 (d, J=6.8 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.15 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 4) Rt=1.601 min.; MS m/z: 371 [M+H]+. SFC (Table 1, Method 24) Rt=7.354 min.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 0.5 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was purified by prep-TLC (eluting with 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-6ba2ca5446b34a74b2740d8ad4a2a2af
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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