Ammonia → HCID 89689760, compound

HRID 595401Notes

Reaction equation

HRID 595401 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22]([O:24]CC)=O)[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:30])[CH3:29])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[NH3:31]>CO>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22]([NH2:31])=[O:24])[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:29])[CH3:30])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 89689564HCID 89689564, compound

Product 1

HCID 89689760HCID 89689760, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

The ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxylate (Example 20) (200 mg, 0.455 mmol) was taken in a sealed tube, to it methanol (2 mL) was added, followed by addition of methanolic ammonia (10 mL). The reaction mixture was heated at 80° C. for 3 h. The reaction mixture was concentrated. The crude material was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent. The material obtained was further purified on preparative TLC to obtain 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxamide. 1H NMR: 400 MHz, DMSO-d6: δ 1.33 (d, J=6.40 Hz, 6H), 3.64-3.72 (m, 1H), 6.15 (s, 1H), 7.58 (dd, J=2.00, 8.80 Hz, 1H), 7.63 (bs, 1H), 7.69 (bs, 1H), 7.95 (d, J=8.80 Hz, 1H), 8.14 (s, 1H), 8.32 (s, 1H), 8.35 (d, J=6.80 Hz, 1H), 8.49 (s, 1H), 8.72 (d, J=2.00 Hz, 1H), 9.15 (s, 1H), 9.35 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 1.933 min; LCMS (ES-API), m/z 411.0 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.137 min; Purity: 99.8%.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated
  3. customThe crude material was purified by column chromatography through silica gel and MeOH
  4. customThe material obtained
  5. customwas further purified on preparative TLC

Sources & evidence

ORD record
ord-db16168010354355a6b3b613700b090c
Source dataset
uspto-grants-2016_01
Patent number
US09242975B2

Reaction notes

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