Morpholine → HCID 59700221, compound

HRID 2234625Notes

Reaction equation

HRID 2234625 reaction equation
[N:1]([C:4]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])=[CH:22][N:21](S(C4C=CC(C)=CC=4)(=O)=O)[C:18]3=[N:19][CH:20]=2)=[CH:11][C:5]=1[C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[C:2]=[O:3].[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>C(Cl)Cl>[CH3:10][N:8]([CH3:9])[C:6]([C:5]1[CH:11]=[C:12]([C:15]2[CH:16]=[C:17]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])=[CH:22][NH:21][C:18]3=[N:19][CH:20]=2)[CH:13]=[CH:14][C:4]=1[NH:1][C:2]([N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1)=[O:3])=[O:7]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 597002582-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

Product 1

HCID 59700221HCID 59700221, compoundYield 24.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 3 mL reaction vial were added 2-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (48 mg, 0.085 mmol), methylene chloride (1 mL) and morpholine (40 μL, 0.455 mmol, pre-treated with molecular sieves). The solution was stirred at room temperature for at least 12 h and monitored by HPLC. The reaction mixture was concentrated then re-dissolved in MeOH (1 mL), and cooled to 0° C. and treated with 100 μL 50% (w/w) aqueous KOH for 30 min or until Ts-removal was complete. The reaction was quenched by addition of 500 μL glacial acetic acid and then concentrated in vacuum. Purification by Mass-triggered HPLC (formic acid ACN/H2O gradient) followed by lyophilization provided 10.4 mg of the title compound as a white powder. 1H-NMR (500 MHz, d6-DMSO) δ 11.91 (br.s, 1H), 8.73 (br.s., 1H), 8.52 (d, J=2.0 Hz, 1H), 8.14 (d, J=2.0 Hz, 1H), 7.71 (m, 3H), 7.80 (s, 1H), 7.58 (d, J=9.0 Hz, 1H), 7.28 (app t, J=7.5 Hz, 1H), 7.11 (d, J=7 Hz, 1H), 7.03 (t, J=7 Hz, 1H), 3.80 (s, 3H), 3.60 (m, 4H), 3.51 (m, 4H), 2.96 (br s, 6H); MS: m/z 500.1 [M+H+].

Workup

  1. customInto a 3 mL reaction
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthen re-dissolved in MeOH (1 mL)
  4. temperaturecooled to 0° C.
  5. additiontreated with 100 μL 50% (w/w) aqueous KOH for 30 min or until Ts-removal
  6. customThe reaction was quenched by addition of 500 μL glacial acetic acid
  7. concentrationconcentrated in vacuum
  8. customPurification by Mass-triggered HPLC (formic acid ACN/H2O gradient)

Sources & evidence

ORD record
ord-671caacabf5f4ae7b5c0b1028ea239c3
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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