1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amide

HRID 79054Notes

Reaction equation

HRID 79054 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:15]([C:16]([OH:18])=O)=[CH:14][N:13]=[C:12]2[N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[N:20]=[CH:21][C:11]=12.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:53][O:54][CH2:55][C@@H:56]([OH:58])[CH3:57].CCN(C(C)C)C(C)C>CN(C=O)C.O>[OH:58][C@@H:56]([CH3:57])[CH2:55][O:54][NH:53][C:16]([C:15]1[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[C:11]2[CH:21]=[N:20][N:19]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)[C:12]2=[N:13][CH:14]=1)=[O:18]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67083983HCID 67083983, compoundHCID 86637725(S)-1-aminooxypropan-2-ol hydrochloride

Product 1

HCID 866562434-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amideYield 60.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (728 mg, 1.4 mmol), HOBt (228 mg, 1.7 mmol) and EDCI (323 mg, 1.7 mmol) in DMF (15 mL) was added a solution of (S)-1-aminooxypropan-2-ol hydrochloride (200 mg, 1.5 mmol), and DIPEA (596 μL, 3.5 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 3 hours then diluted with water (30 mL) and the aqueous layer extracted with dichloromethane (3×20 mL). The combined organic extracts were filtered through a hydrophobic frit and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as a cream solid (500 mg, 60%). LCMS (Method B): RT=3.23 min, [M+H]+=592.

Workup

  1. extractionthe aqueous layer extracted with dichloromethane (3×20 mL)
  2. filtrationThe combined organic extracts were filtered through a hydrophobic frit
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c5c49e4a083f42f1b7d7bb8b94b42d57
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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