Pyridine → HCID 135931653, compound

HRID 1056809Notes

Reaction equation

HRID 1056809 reaction equation
[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[C:8]([C:12]([OH:14])=O)=[CH:7][NH:6][C:5]=2[S:4][N:3]=1.[C:15]([C:19]1[C:27]2[C:22](=[CH:23][C:24]([NH2:28])=[CH:25][CH:26]=2)[NH:21][CH:20]=1)([CH3:18])([CH3:17])[CH3:16].N1C=CC=CC=1>C(OCC)(=O)C>[C:15]([C:19]1[C:27]2[C:22](=[CH:23][C:24]([NH:28][C:12]([C:8]3[C:9](=[O:11])[C:10]4[C:2]([CH3:1])=[N:3][S:4][C:5]=4[NH:6][CH:7]=3)=[O:14])=[CH:25][CH:26]=2)[NH:21][CH:20]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 1049PyridineHCID 574701993-(tert-Butyl)-1h-indol-6-amineHCID 1357416853-Methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxylic acid

Product 1

HCID 135931653HCID 135931653, compoundYield 33.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

3-Methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxylic acid (100.0 mg, 475.7 μmol) and 3-tert-butyl-1H-indol-6-amine (89.56 mg, 0.4757 mmol) were added to a 20-mL vial and suspended in 2-methyl THF (1 mL), followed by propane phosphonic acid anhydride (T3P®, 50% solution in ethyl acetate, 757 mg, 1.19 mmol). Pyridine (75.26 mg, 76.95 μL, 951.4 μmol) was then added and the solution heated at 45° C. for 16 h. The reaction was diluted with 5 mL ethyl acetate and washed with water (1×10 mL). The organic layer was pulled off and concentrated. The residue was dissolved in 6 mL DMF and HPLC purified (RP-C18, 20-99% CH3CN/0.05% TFA). The pooled product fractions were concentrated to approximately 5 mL to provide a suspended white solid. The suspended material was filtered, washed with water and air dried to yield the product N-(3-tert-butyl-1H-indol-6-yl)-3-methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxamide (60 mg, 33% yield) as an off-white solid. LC/MS m/z 381.0 [M+H]+, retention time 1.79 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min). 1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 12.27 (s, 1H), 10.73 (s, 1H), 8.92 (s, 1H), 8.11 (d, J=1.7 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 7.02 (dd, J=9.5, 0.9 Hz, 1H), 6.98 (d, J=2.3 Hz, 1H), 2.79 (s, 3H), 1.40 (s, 9H).

Workup

  1. washwashed with water (1×10 mL)
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in 6 mL DMF
  4. customHPLC purified (RP-C18, 20-99% CH3CN/0.05% TFA)
  5. concentrationThe pooled product fractions were concentrated to approximately 5 mL
  6. customto provide a suspended white solid
  7. filtrationThe suspended material was filtered
  8. washwashed with water and air
  9. customdried

Sources & evidence

ORD record
ord-fde556d2d8e943818ef0489e8b00fcdd
Source dataset
uspto-grants-2016_07
Patent number
US09399648B2

Reaction notes

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