Diisopropylethylamine → HCID 25060284, compound

HRID 2234682Notes

Reaction equation

HRID 2234682 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].C(N(CC)C(C)C)(C)C.[CH2:51]([N:53]1[CH2:57][CH2:56][CH:55]([OH:58])[CH2:54]1)[CH3:52]>C(Cl)Cl>[CH2:51]([N:53]1[CH2:57][CH2:56][CH:55]([O:58][C:2](=[O:3])[NH:1][C:4]2[CH:14]=[CH:13][C:12]([C:15]3[CH:16]=[C:17]4[C:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][CH3:31])=[CH:22][NH:21][C:18]4=[N:19][CH:20]=3)=[CH:11][C:5]=2[C:6](=[O:7])[N:8]([CH3:9])[CH3:10])[CH2:54]1)[CH3:52]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 982031-Ethyl-3-pyrrolidinolHCID 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 25060284HCID 25060284, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (125 mg, 0.22 mmol), N,N-diisopropylethylamine (0.06 mL, 0.34 mmol), 1-ethyl-pyrrolidin-3-ol (253 mg, 2.2 mmol), and methylene chloride (3 mL) were combined and stirred at room temperature for 18 hours. The reaction was concentrated to dryness in vacuo. The crude material was dissolved in a solution of tetrahydrofuran (4 mL) and methanol (1 mL). To the mixture was added 0.2 mL 50% w/v aqueous potassium hydroxide and the combined mixture stirred for 30 minutes. The reaction was quenched with saturated sodium bicarbonate, and the mixture was extracted with methylene chloride. The organic layer was dried over sodium sulfate and concentrated to dryness in vacuo. The crude material was purified by preparative HPLC to give 25 mg (47 μmol, 22%) of {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-carbamic acid 1-ethyl-pyrrolidin-3-yl ester. 1H-NMR (250 MHz, CDCl3) δ 11.93 (s, 1H), 9.10 (s, 1H), 8.64 (d, J=1.9 Hz, 1H), 8.16 (d, J=2.1 Hz, 1H), 7.75-7.54 (m, 5H), 7.30 (t, J=7.1 Hz, 1H), 7.13 (d, J=7.9 Hz, 1H), 7.05 (t, J=7.5 Hz, 1H), 5.10-5.02 (m, 1H), 3.82 (s, 3H), 2.97 (s, 3H), 2.93 (s, 3H), 2.77-2.24 (m, 7H), 1.80-1.72 (m, 1H), 1.03 (t, J=7.2 Hz, 3H); MS: m/z 528.3 (M+H+).

Workup

  1. concentrationThe reaction was concentrated to dryness in vacuo
  2. dissolutionThe crude material was dissolved in a solution of tetrahydrofuran (4 mL) and methanol (1 mL)
  3. additionTo the mixture was added 0.2 mL 50%
  4. stirringthe combined mixture stirred for 30 minutes
  5. customThe reaction was quenched with saturated sodium bicarbonate
  6. extractionthe mixture was extracted with methylene chloride
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated to dryness in vacuo
  9. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-7a44fe4739364e4a865b0811ff62f13b
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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