Methanol → HCID 11374592, compound

HRID 1172565Notes

Reaction equation

HRID 1172565 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:27][N:7]2[CH2:8][CH2:9][N:10]([C:12]3[N:17]=[C:16]([NH2:18])[N:15]4[N:19]=[C:20]([C:22]5[O:23][CH:24]=[CH:25][CH:26]=5)[N:21]=[C:14]4[N:13]=3)[CH2:11][CH:6]2[CH2:5][CH2:4]1.[N:28]1[CH:33]=[CH:32][C:31]([CH:34]=O)=[CH:30][CH:29]=1.CO.[BH4-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[O:23]1[CH:24]=[CH:25][CH:26]=[C:22]1[C:20]1[N:21]=[C:14]2[N:13]=[C:12]([N:10]3[CH2:9][CH2:8][N:7]4[CH2:27][CH:3]([CH2:2][NH:1][CH2:34][C:31]5[CH:32]=[CH:33][N:28]=[CH:29][CH:30]=5)[CH2:4][CH2:5][CH:6]4[CH2:11]3)[N:17]=[C:16]([NH2:18])[N:15]2[N:19]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 133894-PyridinecarboxaldehydeHCID 4311764Sodium borohydrideHCID 11152880HCID 11152880, compound

Product 1

HCID 11374592HCID 11374592, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (7RS,9aRS)-5-(7-aminomethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (1 eq.; see Example 9 above) and pyridine-4-carbaldehyde (1 eq.) in anhydrous THF was treated with titanium (IV) isopropoxide (1.7 eq.) at around 60° C. for 5 hours. To the mixture was added anhydrous methanol, and followed by the careful addition of NaBH4 (1.5 eq). After one hour, the reaction was completed as indicated by HPLC analysis. The solvent was removed and the residue was purified by preparative HPLC using aqueous CH3CN (buffered with 0.1% TFA) to afford (7RS,9aRS)-2-furan-2-yl-5-(7-{[(pyridin-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine as a white powder: 1H NMR (400 MHz, CD3OD) δ 1.77-2.11 (m, 4H), 2.66 (m, 1H), 3.78-3.05 (m, 1H), 4.46 (bs, 2H), 6.65 (dd, J=1.8, 3.4 Hz, 1H), 7.18 (d, J=3.4 Hz, 1H), 7.74 (d, J=1.8 Hz, 1H), 7.88 (d, J=6.0 Hz, 2H), 8.81 (d, J=6.0 Hz, 2H). MS m/z: 461 [M+H]+.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9c7ce0460da44249afe39b632e3798a5
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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