Dietylaminopropin → N-(4-(2-(3-(diethylamino)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676245Notes

Reaction equation

HRID 1676245 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH2:35]([N:37]([CH2:41][CH3:42])[CH2:38][C:39]#[CH:40])[CH3:36]>>[CH2:35]([N:37]([CH2:41][CH3:42])[CH2:38][C:39]#[C:40][C:16]1[S:17][C:10]2[C:11](=[N:12][CH:13]=[CH:14][C:9]=2[O:8][C:7]2[CH:6]=[CH:5][C:4]([N:19]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:20]([C:22]3([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]3)=[O:21])=[CH:3][C:2]=2[F:1])[CH:15]=1)[CH3:36]

Participants

3

Reactant 2

HCID 20010DietylaminopropinHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67349599N-(4-(2-(3-(diethylamino)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Conditions

Temperature
50 °C

Procedure

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl) -N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (500 mg, 0.845 mmol) and N, N-diethylprop-2-yn-1-amine (118 mg, 1.06 mmol) according to the procedure described for Example 6, Step B, except the reaction was heated at 50° C. for 1 hour. The crude was purified by two successive Biotage 40M silica gel columns eluting with 5% MeOH in EtOAc, and then on a second column with 5% MeOH (containing 7N NH3) in CHCl3. Yield: 115 mg (24%). 1H NMR (400 MHz, CDCl3) δ 10.15 (s, 1H), 8.47 (m, 2H), 7.77 (m, 1H), 7.55 (s, 1H), 7.45 (m, 2H), 7.20 (m, 2H), 7.05 (m, 2H), 6.50 (d, J=5 Hz, 1H), 3.71 (s, 2H), 2.65 (m, 4H), 1.78 (m, 2H), 1.62 (m, 2H), 1.13 (m, 6H). LRMS (APCI pos) m/e 575 (M+1). HPLC: 99% purity (220 nm).

Workup

  1. customThe crude was purified by two successive Biotage 40M silica gel columns
  2. washeluting with 5% MeOH in EtOAc

Sources & evidence

ORD record
ord-57cb433dc42047ac8ae84b806c8679fe
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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