Trifluoroacetic acid → HCID 11374270, compound

HRID 1172563Notes

Reaction equation

HRID 1172563 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:14][C@H:15]([CH2:18][NH:19][C:20]3[N:25]=[C:24]([NH2:26])[N:23]4[N:27]=[C:28]([C:30]5[O:31][CH:32]=[CH:33][CH:34]=5)[N:29]=[C:22]4[N:21]=3)[CH2:16][CH2:17][C@@H:10]2[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.ClC1[N:48]=[CH:47][CH:46]=[CH:45][N:44]=1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[O:31]1[CH:32]=[CH:33][CH:34]=[C:30]1[C:28]1[N:29]=[C:22]2[N:21]=[C:20]([NH:19][CH2:18][CH:15]3[CH2:14][N:11]4[CH2:12][CH2:13][N:8]([C:6]5[N:48]=[CH:47][CH:46]=[CH:45][N:44]=5)[CH2:9][CH:10]4[CH2:17][CH2:16]3)[N:25]=[C:24]([NH2:26])[N:23]2[N:27]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 86613762HCID 86613762, compound

Product 1

HCID 11374270HCID 11374270, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-7-[(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino)-methyl]-octahydro-pyrido[1,2-a]pyrazine-2-carboxylic acid tert-butyl ester (1 eq., see Example 7(b) above) in methylene chloride was added trifluoroacetic acid to reach a final concentration of 10% TFA. The mixture was stirred at room temperature for 2 hours, after which the solvent was removed under reduced pressure, and the residue was dissolved in acetonitrile. To the resulting solution was added 2-chloropyrimidine (1 eq.) and Na2CO3 (2 eq.). The mixture was stirred at around 80° C. for overnight. The solvent was removed afterwards, and the residue was purified by preparative HPLC using aqueous CH3CN (buffered with 0.1% TFA) to afford (7RS,9aSR)-2-furan-2-yl-N5-(2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine. 1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J=4.7 Hz, 2H), 7.70 (d, J=2 Hz, 1H), 7.12 (d, J=3.6 Hz, 1H), 6.72 (t, J=4.7 Hz, 1H), 6.62 (dd, J=2, 3.6 Hz, 1H), 4.97 (d, J=14.1 Hz, 2H), 3.34-3.58 (m, 4H), 3.11-3.24 (m, 3H), 2.82-3.03 (m, 2H), 2.33 (m, 1H), 2.10 (d, J=14.1 Hz, 1H), 2.02 (d, J=13.2 Hz, 1H), 1.60-1.69 (m, 1H), 1.39-1.49 (m, 1H). MS m/z: 448[M+H]+.

Workup

  1. customafter which the solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in acetonitrile
  3. stirringThe mixture was stirred at around 80° C. for overnight
  4. customThe solvent was removed afterwards
  5. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1ce586ff87ed4521972f36609239bb4f
Source dataset
uspto-grants-2010_11
Patent number
US07834014B2

Reaction notes

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