Diisopropylethylamine → HCID 60209292, compound

HRID 2237317Notes

Reaction equation

HRID 2237317 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-8f4ff389971c4c1189eb179aaa7a872e
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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