HCID 60768076, compound → HCID 67347067, compound

HRID 1676303Notes

Reaction equation

HRID 1676303 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.[CH3:35][N:36]([CH3:46])[CH:37]1[CH2:42][CH2:41][N:40]([CH2:43][C:44]#[CH:45])[CH2:39][CH2:38]1>>[CH3:35][N:36]([CH3:46])[CH:37]1[CH2:38][CH2:39][N:40]([CH2:43][C:44]#[C:45][C:16]2[S:17][C:10]3[C:11](=[N:12][CH:13]=[CH:14][C:9]=3[O:8][C:7]3[CH:6]=[CH:5][C:4]([N:19]([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[C:20]([C:22]4([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]4)=[O:21])=[CH:3][C:2]=3[F:1])[CH:15]=2)[CH2:41][CH2:42]1

Participants

3

Reactant 2

HCID 60768076HCID 60768076, compoundHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67347067HCID 67347067, compoundYield 7.5%

Procedure

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 50 mg, 0.0845 mmol) and N,N-dimethyl-1-(prop-2-ynyl)piperidin-4-amine (Example 20, Step A, 35.1 mg, 0.211 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.32), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was further purified by trituration with 3:1 pentane/DCM (5 mL) and filtered. The product was obtained as a waxy solid (4 mg, 7%). HPLC: 100% purity (220 nm); LCMS (APCI+): 100% purity, 220 nm, m/z 630 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.49 (m, 1H), 8.17 (br s, 1H), 7.77 (m, 1H), 7.59 (s, 1H), 7.45 (m, 2H), 7.26 (m, 2H, overlaps chloroform), 7.07 (m, 2H), 6.51 (m, 1H), 3.59 (s, 2H), 3.02 (m, 2H), 2.30 (m, 9H), 1.82 (m, 4H), 1.62 (m, 4H).

Workup

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.32)
  2. washeluting with 10% MeOH (containing 7N NH3) in CHCl3
  3. customThe product was further purified by trituration with 3:1 pentane/DCM (5 mL)
  4. filtrationfiltered

Sources & evidence

ORD record
ord-62316e88a39b43e9901db184f6e5aa66
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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