Cyclopropylamine → 1-(4-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea

HRID 409967Notes

Reaction equation

HRID 409967 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[N:11][CH:12]=1.CC[N:33]([CH:37](C)C)[CH:34]([CH3:36])[CH3:35].ClC(Cl)([O:43]C(=O)OC(Cl)(Cl)Cl)Cl.C1(N)CC1>O1CCCC1>[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH:27][C:37]([NH:33][CH:34]4[CH2:35][CH2:36]4)=[O:43])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[N:11][CH:12]=1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 579672584-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

Product 1

HCID 442299041-(4-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylureaYield 230.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL round bottom flask was charged with 319 (0.55 g, 1.3 mmol) and DIPEA (0.91 mL, 5.2 mmol) in dry tetrahydrofuran (55 mL) to give a colorless solution. The reaction mixture was cooled to 0° C. then triphosgene (0.154 g, 0.520 mmol) was added. The reaction mixture was stirred for 1 h at 0° C. then cyclopropylamine (1.8 mL, 26 mmol) was added. Finally the reaction mixture was stirred at r.t. for 3 h then concentrated. The residue was partitioned between water and ethyl acetate, resulting in the formation a thick white solid. This was isolated by suction filtration, rinsed with water and ethyl acetate, and dried in vacuo to give crude 320 (0.65 g, 1.2 mmol, 99% yield) which was used without further purification. MS: 507.2 (M+H).

Workup

  1. customto give a colorless solution
  2. stirringFinally the reaction mixture was stirred at r.t. for 3 h
  3. concentrationthen concentrated
  4. customThe residue was partitioned between water and ethyl acetate
  5. customresulting in the formation a thick white solid
  6. customThis was isolated by suction filtration
  7. washrinsed with water and ethyl acetate
  8. customdried in vacuo

Sources & evidence

ORD record
ord-ba7db4bf9ca24d3aa11d02a9b2a8b9af
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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