1-Hydroxybenzotriazole → 5-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

HRID 450132Notes

Reaction equation

HRID 450132 reaction equation
[Cl:1][C:2]1[C:3]([C:20]([OH:22])=O)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])[N:5]2[C:10]=1[CH:9]=[CH:8][N:7]=[CH:6]2.[CH3:23][C:24]1([CH3:32])[O:28][C@@H:27]([CH2:29][O:30][NH2:31])[CH2:26][O:25]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:23][C:24]1([CH3:32])[O:28][C@@H:27]([CH2:29][O:30][NH:31][C:20]([C:3]2[C:2]([Cl:1])=[C:10]3[CH:9]=[CH:8][N:7]=[CH:6][N:5]3[C:4]=2[NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[O:22])[CH2:26][O:25]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 672348605-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid

Product 1

HCID 867619445-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amideYield 29.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (145 mg, 0.34 mmol), O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (50 mg, 0.34 mmol), HOBt (50 mg, 0.37 mmol), EDCI hydrochloride (71 mg, 0.37 mmol) and DIPEA (63 μL, 0.37 mmol) were dissolved in DMF (3 mL). The reaction was stirred at room temperature for 3 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 25-100% ethylacetate in cyclohexane) to yield the title compound as a brown solid (57 mg, 25%). LCMS (Method B): RT=3.63 min, M+H+=561.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3a1eee3ef1d244b7a541dd9bd886223c
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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