Diisopropylethylamine → 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

HRID 2264976Notes

Reaction equation

HRID 2264976 reaction equation
[CH:1]1([N:4]2[C:12]3[CH:11]=[CH:10][N:9]=[CH:8][C:7]=3[C:6]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=3[F:21])=[C:5]2[C:22](O)=[O:23])[CH2:3][CH2:2]1.[CH3:25][C:26]1([CH3:34])[O:30][CH:29]([CH2:31][O:32][NH2:33])[CH2:28][O:27]1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:25][C:26]1([CH3:34])[O:30][CH:29]([CH2:31][O:32][NH:33][C:22]([C:5]2[N:4]([CH:1]3[CH2:2][CH2:3]3)[C:12]3[CH:11]=[CH:10][N:9]=[CH:8][C:7]=3[C:6]=2[NH:13][C:14]2[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=2[F:21])=[O:23])[CH2:28][O:27]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10240948O-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]hydroxylamineHCID 595964661-Cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

Product 1

HCID 595965981-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a heterogeneous mixture of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (160.0 mg, 0.37 mmol) and O-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (113.1 mg, 0.77 mmol, 2.1 eq) in anhydrous N,N-dimethylformamide (5.7 mL) was added N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (278.3 mg, 0.74 mmol, 2.0 eq) and N,N-diisopropylethylamine (0.25 mL, 1.46 mmol, 4.0 eq), and the resulting homogeneous reaction mixture was stirred under N2 at RT for 16 h. The reaction mixture was quenched with MeOH (2 mL), and the crude material was absorbed onto silica. The crude mixture was purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% EtOAc in hexane) to afford the product as an orange waxy solid (75.4 mg; 36.4%). LC-MS (method C): [M+H]+=567.2, RT=0.73 min.

Workup

  1. customThe reaction mixture was quenched with MeOH (2 mL)
  2. customthe crude material was absorbed onto silica
  3. customThe crude mixture was purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% EtOAc in hexane)
  4. customto afford the product as an orange waxy solid (75.4 mg; 36.4%)

Sources & evidence

ORD record
ord-d46febb2b98c44aebb73ef2be1279d49
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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