Dimethylformamide → 3-(4-Methyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide bis(trifluoroacetate)

HRID 1894871ノート

反応式

HRID 1894871 の反応式
[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:8]=[C:9]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[C:10]([OH:12])=O)[CH:6]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)[O:30]N1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:53][C:54]1[CH:60]=[CH:59][C:57]([NH2:58])=[CH:56][C:55]=1[C:61]1[CH:69]=[C:68]2[C:64]([C:65]3[CH:73]=[N:72][CH:71]=[N:70][C:66]=3[NH:67]2)=[CH:63][CH:62]=1.CN([CH:77]=[O:78])C>>[F:17][C:16]([F:19])([F:18])[C:77]([OH:78])=[O:30].[F:17][C:16]([F:19])([F:18])[C:77]([OH:78])=[O:30].[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:8]=[C:9]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[C:10]([NH:58][C:57]2[CH:59]=[CH:60][C:54]([CH3:53])=[C:55]([C:61]3[CH:69]=[C:68]4[C:64]([C:65]5[CH:73]=[N:72][CH:71]=[N:70][C:66]=5[NH:67]4)=[CH:63][CH:62]=3)[CH:56]=2)=[O:12])[CH:6]=1

参加物

6

反応物 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 469002413-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acidHCID 690464994-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)aniline

生成物 1

HCID 866219583-(4-Methyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide bis(trifluoroacetate)

実験手順

To 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)benzoic acid (39 mg, 0.14 mmol, prepared according to WO2004005281) was added DMF (0.93 mL) followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (66.5 mg, 0.175 mmol) and N,N-diisopropylethylamine (DIPEA) (30.5 μL, 0.175 mmol). This solution was stirred at ambient temperature for 15 minutes, then 4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)aniline (40.0 mg, 0.146 mmol) was added. The reaction was held at ambient temperature until LCMS indicated complete reaction, typically 1-2 hours. The reaction was partitioned between water and EtOAc and the organic phase was washed with water and saturated aqueous NaCl, then dried (MgSO4) and evaporated to dryness to leave the crude product. This was purified by preparative LCMS to recover the product as a bis-TFA salt (60.3 mg, 55%). 1H NMR (400 MHz, DMSO): δ 13.0 (bs, 1H), 10.67 (s, 1H), 9.63 (s, 1H), 9.60 (s, 1H), 9.12 (s, 1H), 8.60 (s, 1H), 8.42 (m, 2H), 8.37 (d, 1H), 8.15 (s, 1H), 7.77 (m, 2H), 7.56 (s, 1H), 7.43 (dd, 1H), 7.37 (d, 1H), 2.33 (s, 3H), 2.26 (s, 3H). MS (EI) m/z=527 (M+H).

後処理

  1. customwas held at ambient temperature until LCMS
  2. customreaction, typically 1-2 hours
  3. customThe reaction was partitioned between water and EtOAc
  4. washthe organic phase was washed with water and saturated aqueous NaCl
  5. dry with materialdried (MgSO4)
  6. customevaporated to dryness

出典と根拠

ORDレコード
ord-59020a56a9734ee08655758be62c85ca
出典データセット
uspto-grants-2013_08
特許番号
US08513270B2

反応ノート

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