Trifluoroacetic acid → 4-Methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[5-(trifluoromethyl)pyridin-3-yl]benzamide

HRID 77722

반응식

HRID 77722 반응식
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]1[CH:19]=[C:18]2[C:14]([C:15]3[CH:23]=[N:22][CH:21]=[N:20][C:16]=3[NH:17]2)=[CH:13][CH:12]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[F:48][C:49]([F:58])([F:57])[C:50]1[CH:51]=[C:52]([NH2:56])[CH:53]=[N:54][CH:55]=1.C(O)(C(F)(F)F)=O.F[P-](F)(F)(F)(F)F>CC#N.O.CN(C=O)C>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:56][C:52]2[CH:53]=[N:54][CH:55]=[C:50]([C:49]([F:58])([F:48])[F:57])[CH:51]=2)=[O:8])=[CH:4][C:3]=1[C:11]1[CH:19]=[C:18]2[C:14]([C:15]3[CH:23]=[N:22][CH:21]=[N:20][C:16]=3[NH:17]2)=[CH:13][CH:12]=1

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 9886HexafluorophosphateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 140519365-(Trifluoromethyl)pyridin-3-amineHCID 690470684-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzoic acid

생성물 1

HCID 251512884-Methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[5-(trifluoromethyl)pyridin-3-yl]benzamide수율 20%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

To a vial was added 4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzoic acid (15.2 mg, 0.0501 mmol), DMF (0.32 mL), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (22.9 mg, 0.0601 mmol). This mixture was stirred 15 min at RT. To the mixture was then added 5-(trifluoromethyl)pyridin-3-amine (10.6 mg, 0.0651 mmol. The resulting mixture was stirred at 70° C. for 18 h. LCMS indicated complete consumption of the activated ester (M+H 422) and showed product (M+H 448). The product was isolated by prep HPLC/MS using a 19 mm×100 mm C18 column; 28% CH3CN—H2O (0.1% TFA), 1 min, to 48% at 6 min; 30 mL/min. The HPLC fractions containing the product were freeze dried to yield a light yellow solid, 5.6 mg, 20% yield. FMR showed that it was the mono TFA salt; and contained some residual PF6. 1H NMR (DMSO-d6) δ 13.29 (s, 1H, NH); 10.76 (s, 1H, amide NH); 9.72 (s, 1H); 9.22 (s, 1H); 9.20 (s, 1H); 8.69 (s, 1H); 8.62 (s, 1H); 8.44 (d, 1H); 7.98 (m, 2H); 7.66 (s, 1H); 7.56 (d, 1H); 7.53 (d, 1H).

후처리

  1. stirringThe resulting mixture was stirred at 70° C. for 18 h
  2. customconsumption of the activated ester (M+H 422)
  3. customThe product was isolated by prep HPLC/MS
  4. additionThe HPLC fractions containing the product
  5. customdried
  6. customto yield a light yellow solid, 5.6 mg, 20% yield

출처 및 근거

ORD 기록
ord-aee36ca7912d4d4e97e530795d1c8f1c
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841318B2

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