Water → HCID 58709822, compound

HRID 2375933Notes

Reaction equation

HRID 2375933 reaction equation
Cl.Cl.Cl.[CH3:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([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:11][CH:12]=2)[CH:7]=[N:6]1.CCN(C(C)C)C(C)C.Cl.[CH3:40][N:41]1[CH2:46][CH2:45][N:44]([C:47](Cl)=[O:48])[CH2:43][CH2:42]1.O>CN(C=O)C>[CH3:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:15]3[C:16]4[CH:23]=[C:22]([C:24]5[CH2:25][CH2:26][N:27]([C:47]([N:44]6[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]6)=[O:48])[CH2:28][CH:29]=5)[NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 30169344-Methylpiperazine-1-carbonyl chloride monohydrochloride3×HCID 69275387HCID 69275387, compound

Product 1

HCID 58709822HCID 58709822, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Conditions

Temperature
0 °C

Procedure

To a suspension of (1-methyl-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine tris-hydrochloride (78.1 mg, 0.172 mmol, 1 eq) in DMF (5 mL), DiPEA (180 μL, 1.0 mmol, 6 eq) was added. After cooling the suspension to 0° C., 4-methyl-1-piperazinecarbonyl chloride hydrochloride (28.6 mg, 0.170 mmol, 1 eq) in DMF (1.5 mL) was added and the reaction was stirred at 0° C. for 2 h. An additional 0.2 eq of 4-methyl-1-piperazinecarbonyl chloride hydrochloride (6.1 mg, 0.036 mmol) in DMF (1 mL) was added and the suspension was stirred again at 0° C. for 3 h. Still additional acid chloride was needed and 4-methyl-1-piperazinecarbonyl chloride hydrochloride (6.1 mg, 0.036 mmol, 0.2 eq) in DMF (1 mL) was added. After 5 h, the reaction was quenched/worked up as follows: reaction solution was added dropwise into water, filtered (M frit), washed with water and then EtOAc, and dried, giving the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ=2.19 (s, 3H), 2.31 (s, br, 4H), 2.44-2.55 (m, 2H), 3.17 (s, br, 4H), 3.40 (t, J=5.2 Hz, 2H), 3.92 (s, br, 2H), 4.03 (s, 3H), 6.38 (s, br, 1H), 6.75 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 8.01 (s, 1H), 8.25 (s, 1H), 8.38 (s, br, 1H), 9.33 (s, —NH), 11.89 (s, —NH). MS (ES+): m/z 472.14 (9) [MH+]. HPLC: tR=1.68 min (ZQ2000, polar—5 min).

Workup

  1. additionwas added
  2. stirringthe suspension was stirred again at 0° C. for 3 h
  3. waitAfter 5 h
  4. customthe reaction was quenched/worked up
  5. customreaction solution
  6. filtrationfiltered (M frit)
  7. washwashed with water
  8. dry with materialEtOAc, and dried

Sources & evidence

ORD record
ord-c0c98db1e66e46c6b581d91f30cec76c
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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