4-Methylmorpholine → 6-Fluoro-7-(2-fluoro-4-iodo-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid (2-tert-butoxy-ethoxy)-amide

HRID 910149Notes

Reaction equation

HRID 910149 reaction equation
[F:1][C:2]1[C:3](=[O:23])[N:4]2[C:8](=[C:9]([C:20]([OH:22])=O)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[F:19])[CH2:7][CH2:6][CH2:5]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:55]([O:59][CH2:60][CH2:61][O:62][NH2:63])([CH3:58])([CH3:57])[CH3:56]>CN(C=O)C>[C:55]([O:59][CH2:60][CH2:61][O:62][NH:63][C:20]([C:9]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[C:2]([F:1])[C:3](=[O:23])[N:4]2[C:8]=1[CH2:7][CH2:6][CH2:5]2)=[O:22])([CH3:58])([CH3:57])[CH3:56]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252657696-Fluoro-7-(2-fluoro-4-iodophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acidHCID 46856370O-(2-tert-butoxyethyl)hydroxylamine

Product 1

HCID 576898066-Fluoro-7-(2-fluoro-4-iodo-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid (2-tert-butoxy-ethoxy)-amideYield 87.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Example 1 (656 mg, 1.52 mmol), HATU (870 mg, 2.28 mmol) and N-Methylmorpholine (835 μL, 7.59 mmol) were stirred in DMF (7.6 mL) at r.t. for 10 min. O-(2-tert-Butoxy-ethyl)-hydroxylamine (303 mg, 2.28 mmol) was added, and the reaction stirred at 70° C. for 16 h. Purification by prep-HPLC gave 730 mg (73%) of compound 4a as a beige solid. MS (ES) [m+H] calc'd for C21H24F2IN3O4, 548. found 548.

Workup

  1. customPurification

Sources & evidence

ORD record
ord-539bd3a4a2a74f5cab3e87ae710319aa
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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