Diisopropylethylamine → 3-Chloro-5-({7-[(2E)-4-(dimethylamino)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenol

HRID 38602

Reaction equation

HRID 38602 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([OH:23])[CH:6]=[C:7]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][NH:21][CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:8]=1.Cl.[CH3:25][N:26]([CH3:33])[CH2:27]/[CH:28]=[CH:29]/[C:30](O)=[O:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.C1COCC1>[Cl:2][C:3]1[CH:4]=[C:5]([OH:23])[CH:6]=[C:7]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][N:21]([C:30](=[O:31])/[CH:29]=[CH:28]/[CH2:27][N:26]([CH3:33])[CH3:25])[CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 668500883-Chloro-5-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride

Product 1

HCID 252210953-Chloro-5-({7-[(2E)-4-(dimethylamino)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-chloro-5-(5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride from Example 65A (150 mg, 0.41 mmol) and (2E)-4-(dimethylamino)but-2-enoic acid hydrochloride from Example 1A (94 mg, 0.57 mmol) in a mixture of DMF (2 mL) and THF (4 mL) was treated with DIPEA (263 mg, 2.03 mmol) and TBTU (197 mg, 0.61 mmol). The mixture was stirred at rt overnight and then directly purified by preparative HPLC. The product was triturated with tert-butyl methyl ether and collected by suction filtration to yield 52 mg (29%) as tan crystals.

Workup

  1. customdirectly purified by preparative HPLC
  2. customThe product was triturated with tert-butyl methyl ether
  3. filtrationcollected by suction filtration
  4. customto yield 52 mg (29%) as tan crystals

Sources & evidence

ORD record
ord-21a6aa94de7b4143a81a33361377c006
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Linked notes

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