Dimethylformamide → HCID 21081740, compound

HRID 347584Notes

Reaction equation

HRID 347584 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][CH:14]=[C:15]([CH2:16][CH2:17][CH2:18][OH:19])[C:8]=23)=[C:4]([F:22])[CH:3]=1.Cl.Cl.[F:25][C:26]1[CH:27]=[C:28](NC(NC(=O)CC2C=CC(F)=CC=2)=S)C=[CH:30][C:31]=1OC1C2=C(C)C(OCCN3CCN(C)CC3)=CN2N=CN=1.CN([C:70]([O:74]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN([CH:97]([CH3:99])[CH3:98])C(C)C.[CH3:100][N:101]([CH:103]=[O:104])[CH3:102]>>[F:22][C:4]1[CH:3]=[C:2]([NH:1][C:70]([C:99]2[C:103](=[O:104])[N:101]([C:102]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=3)[CH:100]=[CH:98][CH:97]=2)=[O:74])[CH:21]=[CH:20][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[NH:13][CH:14]=[C:15]([CH2:16][CH2:17][CH2:18][OH:19])[C:8]=12

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21081593HCID 21081593, compoundHCID 1317262361-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt2×

Product 1

HCID 21081740HCID 21081740, compoundYield 66%

Procedure

To a stirred mixture of 3-(4-(4-amino-2-fluorophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl)propan-1-ol (5 mg, 0.0166 mmol), 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (5.8 mg, 0.025 mmol, Compound B of Example 242), and HATU (Perseptive Biosystems, 10 mg, 0.025 mmol) in DMF (0.5 mL), was added DIPEA (0.1 mL). The reaction mixture was stirred at rt for 2 h and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (6 mg, HCl salt, 66% yield) as a white solid. 1H NMR (CD3OD) δ 8.71 (dd, 1H, J=7.2, 2.0 Hz), 8.22 (d, 1H, J=6.8 Hz), 8.10 (dd, 1H, J=12.4, 2.0 Hz), 8.00 (dd, 1H, J=6.4, 2.0 Hz), 7.25–7.60 (m, 7H), 7.70–7.80 (m, 2H), 3.64 (t, 2H, J=6.4 Hz), 3.05 (t, 2H, J=7.2 Hz), 2.00 (m, 2H); LC/MS ESI+) m/z 517 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-933dbe5ae741489fab131d62862d9159
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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