Hydrochloric Acid → 3-amino-1-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-propan-1-one

HRID 1192413Notes

Reaction equation

HRID 1192413 reaction equation
C(OC(=O)[NH:7][CH2:8][CH:9]([C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:19]3[C:26]([CH3:27])=[CH:25][N:24]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)(=[O:30])=[O:29])[C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:14][CH2:13]1)=[O:11])(C)(C)C.Cl.O>O1CCOCC1.C(OCC)C>[NH2:7][CH2:8][CH:9]([C:37]1[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=1)[C:10]([N:12]1[CH2:13][CH2:14][N:15]([C:18]2[C:19]3[C:26]([CH3:27])=[CH:25][N:24]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)(=[O:30])=[O:29])[C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:16][CH2:17]1)=[O:11]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 68406059[3-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-3-oxo-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 675392393-amino-1-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-propan-1-oneYield 77.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

The [3-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-3-oxo-propyl]-carbamic acid tert-butyl ester (295 mg, 0.464 mmol) was dissolved in 2.3 mL of 1,4-dioxane and treated with 4M HCl in 1,4-dioxane (2.3 mL, 9.29 mmol). The mixture was allowed to stir for 4 hours to completion affording a yellow precipitate. The suspension was diluted with diethyl ether and poured into water. More diethyl ether was added, and the layers were shaken. The ether wash was discarded, and the aqueous was treated with saturated NaHCO3 solution until basic to pH paper (about 10) to afford a white precipitate. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the near-pure 3-amino-1-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-propan-1-one as a colorless oil (194 mg, 77%). 1H NMR (free-base, CDCl3, 400 MHz) δ 8.44 (s, 1H), 8.16 (d, J=8.4 Hz, 2H), 7.59 (t, J=7.2 Hz, 1H), 7.49 (appt, J=7.6 Hz, 2H), 7.31 (m, 3H), 7.19 (d, J=8.0 Hz, 2H), 3.92 (m, 1H), 3.85 (dd, J=8.4, 5.2 Hz, 1H), 3.61 (m, 1H), 3.56-3.50 (m, 4H), 3.43 (m, 2H), 3.32 (m, 2H), 2.90 (m, 2H), 2.29 (s, 3H). LCMS (APCI+) m/z 539 [M+H]+; Rt=2.40 min.

Workup

  1. customaffording a yellow precipitate
  2. stirringthe layers were shaken
  3. washThe ether wash
  4. additionthe aqueous was treated with saturated NaHCO3 solution until basic
  5. customto afford a white precipitate
  6. extractionThe aqueous was extracted with ethyl acetate
  7. washThe organic was washed with water
  8. custombrine, separated
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8304e15060274022b897e74a55e11090
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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