4-Methylbenzylamine → HCID 67479274, compound

HRID 1019658Notes

Reaction equation

HRID 1019658 reaction equation
[CH3:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][CH2:24][CH:23]([C:27]([OH:29])=O)[CH2:22]2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)=[N:6][CH:7]=1.[CH3:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CO>[CH3:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([C:27]([NH:36][CH2:35][C:34]3[CH:37]=[CH:38][C:31]([CH3:30])=[CH:32][CH:33]=3)=[O:29])[CH2:22]2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 660354-MethylbenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67479093HCID 67479093, compound

Product 1

HCID 67479274HCID 67479274, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 8.2 (380 mg, 0.866 mmol), TEA (0.362 mL, 2.60 mmol) and 4-methylbenzylamine (0.331 mL, 2.60 mmol) in DCM (21.7 mL) was added HATU (494 mg, 1.299 mmol). The reaction was stirred at room temperature for 2 hours. The reaction was then concentrated and the residue was adsorbed onto a plug of silica gel and purified by chromatography through a 50 g silica gel column, eluting with 0.5 to 10% MeOH in DCM to give 8 as a stereomeric mixture. This mixture was brought up in a mixture of MeOH and DCM and purified by supercritical fluid chromatography using an ODH (21×250 mm, 5 um) column. The stereoisomer was then resolved with a mixture of 35% MeOH with 0.2% diethylamine going to 40% MeOH with 0.2% diethylamine at 4 minutes with a flow rate of 65 mL per minute to provide 8. 1H NMR (300 MHz, CDCl3) δ ppm 1.61 (br. s., 1H) 1.66-1.81 (m, 1H) 1.81-2.00 (m, 2H) 2.07 (s, 3H) 2.30 (s, 3H) 2.37-2.72 (m, 1H) 2.76-3.12 (m, 1H) 3.16-3.55 (m, 1H) 3.55-3.88 (m, 10H) 3.99 (d, J=11.98 Hz, 1H) 4.13-4.50 (m, 2H) 6.51 (br. s., 1H) 6.84 (s, 2H) 6.95-7.26 (m, 4H) 7.34 (br. s., 1H) 7.85 (s, 1H); M+H 506.27637.

Workup

  1. concentrationThe reaction was then concentrated
  2. custompurified by chromatography through a 50 g silica gel column
  3. washeluting with 0.5 to 10% MeOH in DCM
  4. customto give 8 as a stereomeric mixture
  5. custompurified by supercritical fluid chromatography
  6. additionThe stereoisomer was then resolved with a mixture of 35% MeOH with 0.2% diethylamine going to 40% MeOH with 0.2% diethylamine at 4 minutes with a flow rate of 65 mL per minute
  7. customto provide 8

Sources & evidence

ORD record
ord-c5e3692fd2f9427f88b3a87799c46247
Source dataset
uspto-grants-2014_05
Patent number
US08716281B2

Reaction notes

Loading…