Acetonitrile → N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676304Notes

Reaction equation

HRID 1676304 reaction equation
N[C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:25]=[CH:24][C:19]([C:20]([NH:22][CH3:23])=[O:21])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:28])[CH:3]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]([C:39]2([C:42](F)=[O:43])[CH2:41][CH2:40]2)=[O:38])=[CH:32][CH:31]=1.C(#[N:47])C>>[F:28][C:4]1[CH:3]=[C:2]([N:36]([C:33]2[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=2)[C:37]([C:39]2([C:42]([NH2:47])=[O:43])[CH2:41][CH2:40]2)=[O:38])[CH:27]=[CH:26][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:25]=[CH:24][C:19]([C:20](=[O:21])[NH:22][CH3:23])=[CH:18][CH:17]=3)[S:15][C:8]=12

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 673486984-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamideHCID 866146491-((4-Fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride

Product 1

HCID 67346579N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 64%

Conditions

Temperature
50 °C

Procedure

A 20 mL sealable tube was charged with 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide (Example 95, Step A, 0.240 g, 0.610 mmol), 1-((4-fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride (0.172 g, 0.763 mmol), and acetonitrile (5 mL). The mixture was heated under nitrogen to 50° C. for 12 hours. The reaction was then cooled to room temperature and concentrated to dryness. The crude residue was purified by 3 triturations with hot acetonitrile to obtain product (202 mg, 64%) and as a white solid. LRMS (esi+) 599 m/z (M+1) detected. 1H NMR (d6-DMSO, 400 MHz) δ 10.41 (s, 1H), 10 (s, 1H), 8.55 (m, 2H), 8.20 (s, 1H), 8.00 (m, 5H), 7.64 (m, 2H), 7.52 (m, 2H), 7.16 (m, 2H), 6.65 (m, 1H), 2.82 (d, J=4 Hz, 3H), 1.48 (br s, 4H).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. concentrationconcentrated to dryness
  3. customThe crude residue was purified by 3 triturations with hot acetonitrile

Sources & evidence

ORD record
ord-9295f729cbea4580bf851256df7fda59
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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