Trifluoroacetic acid → N-Benzyl-6-chloro-17-oxa-14-thia-2,4,8,24-tetraazatetracyclo[16.3.1.1(3,7).1(9,13)]tetracosa-1(22),3(24),4,6,9(23),10,12,18,20-nonaene-20-carboxamide Trifluoroacetate

HRID 541942Notes

Reaction equation

HRID 541942 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[NH:6][C:7]3[CH:8]=[C:9]([C:26](O)=[O:27])[CH:10]=[C:11]([CH:25]=3)[O:12][CH2:13][CH2:14][S:15][C:16]3[CH:24]=[C:20]([NH:21][C:22]=1[N:23]=2)[CH:19]=[CH:18][CH:17]=3.[CH2:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:70]([OH:76])([C:72]([F:75])([F:74])[F:73])=[O:71]>CN(C)C=O.CO>[F:73][C:72]([F:75])([F:74])[C:70]([OH:76])=[O:71].[CH2:29]([NH:36][C:26]([C:9]1[CH:10]=[C:11]2[CH:25]=[C:7]([CH:8]=1)[NH:6][C:5]1=[N:23][C:22](=[C:2]([Cl:1])[CH:3]=[N:4]1)[NH:21][C:20]1=[CH:24][C:16](=[CH:17][CH:18]=[CH:19]1)[S:15][CH2:14][CH2:13][O:12]2)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579621096-Chloro-17-oxa-14-thia-2,4,8,24-tetraazatetracyclo[16.3.1.1(3,7).1(9,13)]tetracosa-1(22),3(24),4,6,9(23),10,12,18,20-nonaene-20-carboxylic Acid

Product 1

HCID 69016243N-Benzyl-6-chloro-17-oxa-14-thia-2,4,8,24-tetraazatetracyclo[16.3.1.1(3,7).1(9,13)]tetracosa-1(22),3(24),4,6,9(23),10,12,18,20-nonaene-20-carboxamide TrifluoroacetateYield 16%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 6-chloro-17-oxa-14-thia-2,4,8,24-tetraazatetracyclo[16.3.1.1(3,7).1(9,13)]tetracosa-1(22),3(24),4,6,9(23),10,12,18,20-nonaene-20-carboxylic acid (30 mg, 72 μmol) and benzylamine (12 μL, 0.11 mmol) in N,N-dimethylformamide (1 mL) was treated with N,N-diisopropylethylamine (50 μL, 0.29 mmol) followed by 0.5 M O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate in N,N-dimethylformamide (0.19 mL, 94 μmol) and stirred at 20° C. for 16 h. The reaction mixture was diluted with methanol (4.9 mL) and TFA (0.1 mL) and the resultant suspension was filtered. The filtrate was purified by preparative LCMS to give the desired product (7 mg, 16%) as a solid. LCMS for C26H23ClN5O2S (M+H)+: m/z=503.9. 1H NMR (300 MHz, DMSO-d6): δ 9.66 (s, 1H), 8.91-8.88 (m, 2H), 8.18 (s, 1H), 7.96 (d, J=5.6 Hz, 2H), 7.37-7.21 (m, 9H), 6.94 (s, 1H), 4.41 (d, J=5.9 Hz, 2H), 4.16-4.11 (m, 2H), 3.28-3.23 (m, 2H).

Workup

  1. filtrationthe resultant suspension was filtered
  2. customThe filtrate was purified by preparative LCMS

Sources & evidence

ORD record
ord-8d3d293e6185454fb553c82f2abb9795
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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