Methanol → [4-Chloro-5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-thiazol-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amine

HRID 1754783Notes

Reaction equation

C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:21]3[S:25][C:24]([NH:26][CH2:27][C:28]4[CH:29]=[N:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=4)=[N:23][C:22]=3[Cl:36])=[CH:11]2)(=O)=O)C=CC=CC=1.CO.[OH-].[K+]>C(O)(=O)C>[Cl:36][C:22]1[N:23]=[C:24]([NH:26][CH2:27][C:28]2[CH:29]=[N:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[S:25][C:21]=1[CH2:20][C:12]1[C:13]2[C:14](=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=2)[NH:10][CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-4-chloro-thiazol-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amine 619 was combined with methanol: potassium hydroxide (1M) (1:1, 0.5 mL). The mixture was heated at 80° C. for 2 hours. Acetic acid (0.1 mL) was added and the solvents removed under reduced pressure. The remaining residue was dissolved in dimethylsulfoxide (0.4 mL) and purified by reverse phase HPLC on a Phenomenex column (50 mm×10 mm ID) eluting with 0.1% trifluoroacetic acid in water and 20-100% acetonitrile with 0.1% trifluoroacetic acid over 16 minutes at a flow rate of 6 mL/minute to provide the desired compound P-0190. MS (ESI) [M+H+]+=419.9.

Workup

customthe solvents removed under reduced pressure
dissolutionThe remaining residue was dissolved in dimethylsulfoxide (0.4 mL)
custompurified by reverse phase HPLC on a Phenomenex column (50 mm×10 mm ID)
washeluting with 0.1% trifluoroacetic acid in water and 20-100% acetonitrile with 0.1% trifluoroacetic acid over 16 minutes at a flow rate of 6 mL/minute

Sources & evidence

ORD record: ord-59063fe2c2744df1a3425560706a9f04
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169250B2

Reaction notes

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