Diisopropylethylamine → HCID 60209292, compound

HRID 2374097Notes

Reaction equation

HRID 2374097 reaction equation
N[C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)=[C:4]([F:18])[CH:3]=1.C(OC1C=CC([NH:33]C2N=CN=C(OC3C=CC(NC(=O)CC(NC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1)C1C=CC=CC=1.[F:62][C:63]1[CH:78]=[CH:77][C:66]([CH2:67][NH:68][C:69]([C:71]2([C:74]([OH:76])=O)[CH2:73][CH2:72]2)=[O:70])=[CH:65][CH:64]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:62][C:63]1[CH:64]=[CH:65][C:66]([CH2:67][N:68]([C:2]2[CH:17]=[CH:16][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([C:13](=[O:14])[NH2:15])[CH:8]=3)=[C:4]([F:18])[CH:3]=2)[C:69]([C:71]2([C:74]([NH2:33])=[O:76])[CH2:72][CH2:73]2)=[O:70])=[CH:77][CH:78]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21081526HCID 21081526, compoundHCID 231532054-(4-Amino-2-fluorophenoxy)picolinamideHCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

Product 1

HCID 60209292HCID 60209292, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 49 mg, 0.2 mmol) in DMF (2 mL) at room temperature was added 1-((4-fluorobenzyl)carbamoyl)cyclopropanecarboxylic acid (47 mg, 0.2 mmol), HATU (Perseptive Biosystem, 114 mg, 0.3 mmol), and DIEA (0.2 mL, 1.1 mmol). The reaction mixture was stirred at rt for 2 h, and then quenched by adding 4 mL of methanol. The reaction mixture was purified by prep. HPLC. The desired fractions were combined, neutralized with aq. K2HPO4, and concentrated in vacuo. The solid which formed was collected by filtration (29 mg, 31%). 1H NMR (DMSO-d6) δ 10.78 (br s, 1H), 8.53 (d, 1H, J=5.5 Hz), 8.47 (t, 1H, J=5.5 Hz), 8.11 (s, 1H), 7.88 (dd, 1H, J=13.2, 2.3 Hz), 7.70 (s, 1H), 7.47 (d, 1H, J=9.2 Hz), 7.38 (t, 1H, J=9.2 Hz), 7.34-7.29 (m, 3H), 7.22 (dd, 1H, J=5.5, 2.8 Hz), 7.13 (t, 2H, J=8.8 Hz), 4.30 (d, 2H, J=5.5 Hz), 1.37 (d, 4H, J=10.6 Hz); MS(ESI+) m/z 467.12 (M+H)+.

Workup

  1. customquenched
  2. additionby adding 4 mL of methanol
  3. customThe reaction mixture was purified by prep
  4. concentrationconcentrated in vacuo
  5. customThe solid which formed
  6. filtrationwas collected by filtration (29 mg, 31%)

Sources & evidence

ORD record
ord-1905954d13d14176839ec21c5f7e2b64
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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