Dichloromethane → HCID 25196397, compound

HRID 2374086Notes

Reaction equation

HRID 2374086 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[C:9][C:10]2[N:15]=[CH:14][C:13]([NH:16]C(=O)OC(C)(C)C)=[CH:12][CH:11]=2)=[C:6]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35](=[O:44])[CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[O:33])=[CH:27][C:26]=2[F:45])[CH:5]=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:54]>>[ClH:54].[ClH:54].[NH2:1][C:2]1[C:7]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([NH2:16])=[CH:14][N:15]=2)=[C:6]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35](=[O:44])[CH2:36][C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)=[O:33])=[CH:27][C:26]=2[F:45])[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59852935HCID 59852935, compound

Product 1

HCID 25196397HCID 25196397, compound

Procedure

A solution of tert-butyl 6-(2-(2-amino-4-(2-fluoro-4-(3-(2-(4-fluorophenyl)acetyl)ureido)phenoxy)pyridin-3-yl)ethynyl)pyridin-3-ylcarbamate (23 mg, 0.037 mmol) in CH2Cl2 (2 mL) and treated with TFA (0.5 mL) and stirred at RT for 1 h. The mixture was concentrated in vacuo and the crude product purified by preparative HPLC (Column B) and converted to its hydrochloride salt (11 mg, 52%) in the same manner as Step E of Example 36. 1H NMR (DMSO-d6) δ 11.05 (s, 1H), 10.62 (s, 1H), 8.05 (s, 1H), 7.97 (d, 1H, J=2.7 Hz), 7.94 (d, 1H, J=7.1 Hz), 7.82 (d, 1H, J=12.1 Hz), 7.66 (d, 1H, J=8.8 Hz), 7.45-7.45 (m, 2H), 7.35 (dd, 2H, J=8.2, 5.5 Hz), 7.20 (d, 1H, J=6.6 Hz), 7.16 (t, 2H, J=8.8 Hz), 6.24 (d, 1H, J=6.6 Hz), 3.74 (s, 2H); MS(ESI+): m/z 515.19 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe crude product purified by preparative HPLC (Column B)

Sources & evidence

ORD record
ord-30b1eee718e845caaa76cc8e1dc9f7a1
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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