Ethylamine → HCID 11698415, compound

HRID 2102377Notes

Reaction equation

HRID 2102377 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=4)[NH2:25])=[N:14][CH:13]=[N:12][C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.[CH:29]([N:32]([CH:35](C)C)CC)(C)[CH3:30].ClC(Cl)([O:41]C(=O)OC(Cl)(Cl)Cl)Cl.C(N)C>ClCCl>[CH2:29]([NH:32][C:35]([NH:25][C:24]1[CH:26]=[CH:27][CH:28]=[C:22]([O:21][CH2:20][CH2:19][CH2:18][O:17][C:15]2[C:16]3[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[CH:9][S:10][C:11]=3[N:12]=[CH:13][N:14]=2)[CH:23]=1)=[O:41])[CH3:30]

Participants

6

Reactant 4

HCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 11646895HCID 11646895, compound

Product 1

HCID 11698415HCID 11698415, compoundYield 139.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)aniline (25 mg, 0.063 mmol) and diisopropylethylamine (9.0 mg, 0.069 mmol) in dichloromethane (1.5 mL) was added in three portions over a period of 30 minutes to a solution of triphosgene (7.0 mg, 0.023 mmol) in dichloromethane (0.5 mL) while stirring at ambient temperature. Stirring continued for 15 minutes followed by the addition of ethylamine (0.075 mL, 2M in tetrahydrofuran). The reaction was stirred for 2 hours, then diluted with dichloromethane (30 mL) and washed with sodium bicarbonate (2×20 mL). The organic layer was dried (Na2SO4), concentrated, and purified by column chromatography over silica gel using 40% ethyl acetate in hexanes as eluant to give 15 mg (51%) of N-ethyl-N′-[3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)phenyl]urea as a white solid. MS [M+H] 467.3. 1H NMR (400 MHz, CDCl3) δ (ppm) 8.64 (s, 1H), 7.45-7.38 (m, 2H), 7.21 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.06-7.01 (m, 2H), 6.82 (t, J=2.4 Hz, 1H), 6.79 (m, 1H), 6.50 (m, 1H), 4.58 (t, J=6.0 Hz, 2H), 3.72 (t, J=6.0 Hz, 2H), 3.30 (q, J=7.2 Hz, 2H), 2.06 (m, 2H), 1.16 (t, J=7.2 Hz, 3H).

Workup

  1. stirringStirring
  2. stirringThe reaction was stirred for 2 hours
  3. washwashed with sodium bicarbonate (2×20 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by column chromatography over silica gel using 40% ethyl acetate in hexanes as eluant

Sources & evidence

ORD record
ord-4637457d0966401195a9ba57728b75da
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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