Hydrochloric Acid → HCID 25195744, compound

HRID 1670334Notes

Reaction equation

HRID 1670334 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=2[C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[C:4]([F:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([N:35]=[C:36]=[O:37])=[O:34])=[CH:28][CH:27]=1.COC1C=CC(CNC2N=CN=C(OC3C=CC(NC(NC(=O)CC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1.C(O)(C(F)(F)F)=O.[ClH:83]>>[ClH:83].[ClH:83].[NH2:13][C:9]1[C:8]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[C:7]([O:6][C:5]2[CH:22]=[CH:23][C:2]([NH:1][C:36]([NH:35][C:33](=[O:34])[CH2:32][C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=3)=[O:37])=[CH:3][C:4]=2[F:24])[CH:12]=[CH:11][N:10]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2×HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 59852884HCID 59852884, compound

Product 1

HCID 25195744HCID 25195744, compoundYield 40%

Procedure

The title compound was prepared from 4-(4-amino-2-fluorophenoxy)-3-(2-(pyridin-2-yl)ethynyl)pyridin-2-amine (25 mg, 0.078 mmol) and a 0.3 M solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.26 mL, 0.078 mmol) in the same manner as Step E of Example 11. The crude product was prepared by preparative HPLC (Column B). The TFA salt was converted to the hydrochloride in the same manner as in Step E of Example 36 to give the title compound (18 mg, 40%) as a brown solid. 1H NMR (DMSO-d6) δ 11.06 (s, 1H), 10.63 (s, 1H), 8.62 (d, 1H, J=4.6 Hz), 8.23 (s, 1H), 7.99 (d, 1H, J=7.1 Hz), 7.94-7.84 (m, 3H), 7.87-7.76 (m, 1H), 7.51-7.42 (m, 3H), 7.39-7.32 (m, 2H), 7.21-7.13 (m, 2H), 6.30 (d, 1H, J=7.1 Hz), 3.74 (s, 2H) MS (ESI+): m/z 498.11 (M+H)+.

Workup

  1. customThe crude product was prepared by preparative HPLC (Column B)

Sources & evidence

ORD record
ord-2fbf7b86b9a04a85a56221898f3eb77d
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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