1-Hydroxybenzotriazole → HCID 86654287, compound

HRID 450126Notes

Reaction equation

HRID 450126 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[N:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:13]2=[CH:12][C:11]=1[C:19]([OH:21])=O.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([O:35][NH2:36])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:30][CH2:31][CH:32]([O:35][NH:36][C:19]([C:11]2[CH:12]=[C:13]3[CH:18]=[CH:17][N:16]=[CH:15][N:14]3[C:10]=2[NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[O:21])[CH2:33][CH2:34]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 24729482tert-Butyl 4-(aminooxy)piperidine-1-carboxylateHCID 67235820HCID 67235820, compound

Product 1

HCID 86654287HCID 86654287, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (190 mg, 0.48 mmol), 4-aminooxy-piperidine-1-carboxylic acid tert-butyl ester (154 mg, 0.72 mmol), HOBt (106 mg, 0.79 mmol), EDCI hydrochloride (150 mg, 0.79 mmol) and DIPEA (120 μL, 0.72 mmol) were suspended in DMF (5 mL). The reaction was stirred at RT for 1 hour, during which time the reagents dissolved. The reaction mixture was concentrated in vacuo, the resultant residue 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 0-100% ethylacetate in cyclohexane) to yield the title compound as a brown solid (180 mg, 65%). LCMS (Method B): RT=3.69 min, M+H+−tBu=540 (100%), M+H+−Boc=496 (95%).

Workup

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

Sources & evidence

ORD record
ord-0202bc2aaab1415b8e92317717b1490e
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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