1-Hydroxybenzotriazole → HCID 178434296, compound

HRID 2375923Notes

Reaction equation

HRID 2375923 reaction equation
Cl.Cl.Cl.[CH3:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]3[C:16]4[CH:23]=[C:22]([C:24]5[CH2:25][CH2:26][NH:27][CH2:28][CH:29]=5)[NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=2)[NH:7][N:6]=1.[N:30]1([CH2:36][CH2:37][C:38](O)=[O:39])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[CH3:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]3[C:16]4[CH:23]=[C:22]([C:24]5[CH2:25][CH2:26][N:27]([C:38](=[O:39])[CH2:37][CH2:36][N:30]6[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]6)[CH2:28][CH:29]=5)[NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=2)[NH:7][N:6]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1177821-Piperidinepropanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178434295HCID 178434295, compound

Product 1

HCID 178434296HCID 178434296, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Into the suspension of (3-methyl-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydro pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride (122 mg, 0.190 mmol), 1-piperidinepropanoic acid (48.4 mg, 0.305 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC-HCl) (76.7 mg, 0.400 mmol) and 1-hydroxy benzotriazole (HOBt-H2O) (30.6 mg, 0.200 mmol) in DMF (4.5 mL) was added N,N-diisopropylethylamine (167 μL, 0.952 mmol) under N2 at rt. The reaction mixture, which became a clear wine-red solution, was stirred at rt for 18 h. After that time, the reaction mixture was treated with water/saturated NaHCO3 (5 mL/5 mL) and extracted with EtOAc (4×20 mL). The combined extracts were washed with water (2×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo to obtain a light-brown oil that was purified using the mass-directed purification system to yield the title compound as yellow oil. 1H NMR (CD3OD, 400 MHz): δ=1.69 (brs, 2H), 1.88 (brs, 4H), 2.57 (s, 3H), 2.66 (brs, 2 H), 2.95-3.03 (m, 2H), 3.32 (brs, 4H), 3.41 (t, 2H, J=6.0 Hz), 3.76 (t, 1H, J=5.4 Hz), 3.85 (t, 1H, J=5.6 Hz), 4.28 (brs, 2H), 6.30 (d, 1H, J=2.8 Hz), 6.51-6.55 (m, 1H), 7.49 (d, 1H, J=8.4 Hz), 7.55-7.59 (m, 1H), 7.98-8.00 (m, 1H), 8.19 (s, 1H), 8.42 (s I H). MS (ES+): m/z 485.00 (70) [MH+]. HPLC: tR=1.70 min (ZQ2000, polar—5 min).

Workup

  1. extractionextracted with EtOAc (4×20 mL)
  2. washThe combined extracts were washed with water (2×20 mL) and brine (20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto obtain a light-brown oil that
  7. customwas purified

Sources & evidence

ORD record
ord-4acd38e3c0144185af2d1870bda0b393
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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