1-Hydroxybenzotriazole → HCID 178520818, compound

HRID 2375857Notes

Reaction equation

HRID 2375857 reaction equation
Cl.Cl.Cl.[Cl: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.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl: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

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1177821-Piperidinepropanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178478577HCID 178478577, compound

Product 1

HCID 178520818HCID 178520818, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (3-chloro-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride (46.9 mg, 0.0967 mmol, 1 eq), 1-piperidinepropanoic acid (40.5 mg, 0.255 mmol, 2.6 eq), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (56.2 mg, 0.293 mmol, 3 eq), and 1-hydroxybenzotriazole (HOBt) (13.9 mg, 0.103 mmol, 1 eq) in anhydrous DMF (5 mL), DiPEA (85 μL, 0.48 mmol, 5 eq) was added under an atmosphere of N2 The reaction was stirred at rt for 18 h, after which all solvent was evaporated under reduced pressure. The crude material was adsorbed onto Hydromatrix, dry loaded, and purified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH:DCM 5%→7N NH3/MeOH:DCM 2%→5%→8%→15%]. Fractions 25-39 were combined and concentrated in vacuo, yielding the desired amide, but which contained a considerable amount of 1-(3-dimethylaminopropyl)-3-ethylurea. The yellow solid was triturated in hot MeOH/sonication, giving the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ=1.26 (s, br, 2H), 1.63 (m, 4H), 2.37-2.56 (m, 6H), 2.56-2.68 (m, 2H), 2.68-2.80 (m, 2H), 3.68 & 3.76 (t, J=5.6 Hz, rotamers, 2H), 4.22 & 4.25 (s, br, rotamers, 2H), 5.92 & 5.98 (s, rotamers, 1H), 6.18 & 6.22 (s, br, rotamers, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.79 (dd, J=8.8, 1.6 Hz, 1H), 8.13 (s, 1H), 8.26 (s, 1H). MS (ES+): m/z 505.00/506.99 (27/10) [MH+]; m/z 407.96/409.98 (100/36) [MH+—C6H14N]. HPLC: tR=1.75 min (ZQ2000, polar—5 min).

Workup

  1. additionwas added under an atmosphere of N2 The reaction
  2. customafter which all solvent was evaporated under reduced pressure
  3. customdry loaded
  4. custompurified by chromatography on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with MeOH:DCM 5%→7N NH3/MeOH:DCM 2%→5%→8%→15%]
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6606c60e63204a68bc56a3c4c92c1ef6
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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