Trifluoroacetic acid → HCID 136200180, compound

HRID 929141Notes

Reaction equation

HRID 929141 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][C:9]1[CH:48]=[C:47]([CH3:49])[CH:46]=[CH:45][C:10]=1[O:11][CH2:12][CH:13]([OH:44])[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([O:22]C)[C:17]=1[C:24]1[NH:35][C:34]2[C:26](=[CH:27][C:28]3[CH2:29][N:30]([CH:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)[C:31](=O)[C:32]=3[CH:33]=2)[N:25]=1.CC1C=C(C)C=CC=1OCC(O)CNC1C=CNC(=O)C=1C1NC2C(=CC3CN(C4CCN(C)CC4)C(=O)C=3C=2)N=1.C[Si](C=[N+]=[N-])(C)C>CO.C1COCC1.CC#N>[CH3:8][C:9]1[CH:48]=[C:47]([CH3:49])[CH:46]=[CH:45][C:10]=1[O:11][CH2:12][CH:13]([OH:44])[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][NH:19][C:18](=[O:22])[C:17]=1[C:24]1[NH:35][C:34]2[C:26]([N:25]=1)=[CH:27][C:28]1[CH2:29][N:30]([CH:37]3[CH2:38][CH2:39][N:40]([CH3:43])[CH2:41][CH2:42]3)[CH2:31][C:32]=1[CH:33]=2

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 167693TrimethylsilyldiazomethaneHCID 178426873HCID 178426873, compoundHCID 178494198HCID 178494198, compound

Product 1

HCID 136200180HCID 136200180, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

TFA salt of 2-{4-[3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-methoxy-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one: To a suspension of 2-{4-[3-(2,4-dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one (19 mg, 0.034 mmol) in a mixed solvent of THF/CH3CN (1 mL/1 mL) was added a solution of TMSCH2N2(2.0 M, 2 mL, 4 mmol) at 0° C. After it was stirred at 0° C. for 2 h, the reaction mixture was mixed with MeOH (1 mL), stirred at the room temperature for 22 h, and purified with a preparative TLC plate to furnish a crude which was subjected to HPLC re-purification to afford the title compound in TFA salt form (4.98 mg, 21%). 1H NMR (DMSO-d6) δ 1.92-2.10 (4H), 2.19 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.81 (s, 3H, CH3), 3.20 (m, 2H), 3.40 (s, 3H, OCH3), 3.45-3.55 (3H), 3.68 (m, 1H), 4.00 (s, 2H), 4.12 (m, 1H), 4.30 (m, 1H), 4.43 (s, 1H), 4.48 (s, 1H), 5.47 (br s, 1H, NH), 6.27 (d, J=6 Hz, 1H), 6.82 (d, J=8 Hz, 1H), 6.89-6.97 (2H), 6.98 (s, 1H), 7.15 (s, 0.5H), 7.30 (s, 0.5H), 7.65-7.72 (1.5H), 7.80 (s, 0.5H), 7.95 (s, 0.5H), 9.65 (br s, 1H, NH), 11.11 (br s, 1H, NH); ESI-MS m/z 571.5 (MH+).

Workup

  1. stirringstirred at the room temperature for 22 h
  2. custompurified with a preparative TLC plate
  3. customto furnish a crude which
  4. customre-purification

Sources & evidence

ORD record
ord-d261f42061a3458fb3ba17b3161a1862
Source dataset
uspto-grants-2016_03
Patent number
US09290503B2

Reaction notes

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