Dimethylformamide → N-{6-[5-[(2-Hydroxypropanoyl)amino]-6-(methyloxy)-3-pyridinyl]-1H-indazol-4-yl}-2-methyl-1,3-thiazole-4-carboxamide

HRID 1695785Notes

Reaction equation

HRID 1695785 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([Sn](C)(C)C)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][N:14]3S(C2C=CC=CC=2)(=O)=O)=[O:8])[N:6]=1.Br[C:33]1[CH:34]=[C:35]([NH:41][C:42](=[O:46])[CH:43]([OH:45])[CH3:44])[C:36]([O:39][CH3:40])=[N:37][CH:38]=1.CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[OH:45][CH:43]([CH3:44])[C:42]([NH:41][C:35]1[CH:34]=[C:33]([C:17]2[CH:16]=[C:15]3[C:11]([CH:12]=[N:13][NH:14]3)=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[CH:18]=2)[CH:38]=[N:37][C:36]=1[O:39][CH3:40])=[O:46]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 582558202-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideHCID 67155588N-[5-Bromo-2-(methyloxy)-3-pyridinyl]-2-hydroxypropanamide

Product 1

HCID 44540957N-{6-[5-[(2-Hydroxypropanoyl)amino]-6-(methyloxy)-3-pyridinyl]-1H-indazol-4-yl}-2-methyl-1,3-thiazole-4-carboxamideYield 8.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

2-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (150 mg, 0.267 mmol), N-[5-bromo-2-(methyloxy)-3-pyridinyl]-2-hydroxypropanamide (88 mg, 0.321 mmol) and Pd(PPh3)4 (31 mg, 0.027 mmol) were weighed to a microwave vial. DMF (3 ml) was added and the reaction was heated in the microwave at 120° C. for 30 mins, then again at 120° C. for a further for 30 mins. The reaction mixture was passed through a 1 g silica cartridge, pre-conditioned with methanol, washing with methanol. The solvent was evaporated in the blow down. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (Method E). Pure fraction was evaporated to dryness. The residue was dissolved in IPA and 2M NaOH (aq) and left overnight. The reaction was concentrated in vacuo, then neutralised using 2M HCl (aq) and the resultant precipitate was collected by filtration. The material was dissolved in DMSO:methanol (0.7 ml, 1:1, v/v) and purified by MDAP (Method E). Pure fractions were combined and evaporated to dryness to afford the title compound (10 mg).

Workup

  1. washwashing with methanol
  2. customThe solvent was evaporated in the blow down
  3. dissolutionThe residue was dissolved in DMSO
  4. custommethanol (1 ml, 1:1, v/v) and purified by MDAP (Method E)
  5. customPure fraction was evaporated to dryness
  6. dissolutionThe residue was dissolved in IPA
  7. wait2M NaOH (aq) and left overnight
  8. concentrationThe reaction was concentrated in vacuo
  9. filtrationthe resultant precipitate was collected by filtration
  10. dissolutionThe material was dissolved in DMSO
  11. custommethanol (0.7 ml, 1:1, v/v) and purified by MDAP (Method E)
  12. customevaporated to dryness

Sources & evidence

ORD record
ord-5ee5cbbcdcce4ec9b902d6254ccf5754
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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