Triethylamine → 2-benzyl-5-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one

HRID 1676300Notes

Reaction equation

HRID 1676300 reaction equation
[CH2:1]([C:8]1[NH:13][C:12](=[O:14])[C:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]4[CH:28]=[C:29](I)[S:30][C:23]=34)=[C:17]([F:32])[CH:16]=2)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][C:41]#[CH:42])[CH2:36][CH2:35]1.C(N(CC)CC)C>C1COCC1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([C:8]1[NH:13][C:12](=[O:14])[C:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]4[CH:28]=[C:29]([C:42]#[C:41][CH2:40][N:37]5[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]5)[S:30][C:23]=34)=[C:17]([F:32])[CH:16]=2)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 135140911-Methyl-4-(prop-2-yn-1-yl)piperazineHCID 673469802-benzyl-5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one

Product 1

HCID 589494662-benzyl-5-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-oneYield 83.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-benzyl-5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one (8.0 mg, 0.014 mmol), 1-methyl-4-(prop-2-ynyl)piperazine (Example 17, Step A; 5.0 mg, 0.036 mmol), copper(I) iodide (0.1 mg, 0.0007 mmol), and triethylamine (0.020 ml, 0.14 mmol) in THF (0.5 mL) was sparged with N2 for 5 minutes, and then Pd(PPh3)4 (1.0 mg, 0.0007 mmol) was added. The sealed reaction was stirred at 50° C. for 3 hours. The reaction mixture was purified directly by silica gel chromatography, eluting with 10:1 dichloromethane/methanol. The desired product (6.6 mg, 81%) was obtained as a pale yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 8.58 (d, J=5.5 Hz, 1H), 8.29 (s, 1H), 7.93 (dd, J=1.9, 12.5 Hz, 1H), 7.81 (s, 1H), 7.74 (m, 1H), 7.54 (t, J=8.6 Hz, 1H), 7.39-7.32 (m, 4H), 7.29-7.24 (m, 1H), 6.76 (d, J=5.1 Hz, 1H), 3.94 (s, 2H), 3.68 (s, 2H), 2.55-2.46 (m, 8H), 1.23 (s, 3H). LRMS (ESI pos) m/e 566 (M+1).

Workup

  1. customwas sparged with N2 for 5 minutes
  2. customThe sealed reaction
  3. customThe reaction mixture was purified directly by silica gel chromatography
  4. washeluting with 10:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-5845cd14a42d4fe2ac494a86722952e4
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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