Isopropanol → {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-carbamic acid isopropyl ester

HRID 901570Notes

Reaction equation

HRID 901570 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(C(C)C)C(C)C)C.[CH:51]([OH:54])([CH3:53])[CH3:52]>C(Cl)Cl>[CH:51]([O:54][C:2](=[O:3])[NH: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][NH:21][C:18]3=[N:19][CH:20]=2)=[CH:11][C:5]=1[C:6](=[O:7])[N:8]([CH3:9])[CH3:10])([CH3:53])[CH3:52]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 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 59700218{2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-carbamic acid isopropyl esterYield 48.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 3 mL reation 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 (30 mg, 0.053 mmol), methylene chloride (1 mL), iPr2EtN (21 μL, 0.060 mmol), and isopropyl alcohol (50 μL, 6.5 mmol). 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 12.2 mg of the title compound as a white powder. 1H-NMR (500 MHz, d6-DMSO) δ=11.91 (br.s, 1H), 8.96 (br.s., 1H), 8.53 (d, J=2.0 Hz, 1H), 8.15 (d, J=2.0 Hz, 1H), 7.73 (m, 3H), 7.60 (d, J=9.0 Hz, 1H), 7.59 (s, 1H), 7.29 (dd, J=1.5, 7.2 Hz, 1H), 7.12 (d, J=7 Hz, 1H), 7.04 (t, J=7 Hz, 1H), 4.84 (m, 1H), 3.81 (s, 3H), 2.97, 2,92 (br s, 6H), 1.23 (d, J=6, 6H); MS: m/z 473.1 [M+H+].

Workup

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

Sources & evidence

ORD record
ord-ce92783bea734bc29ea1223a148c7aa3
Source dataset
uspto-grants-2008_04
Patent number
US07361764B2

Reaction notes

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