N-Methylisopropylamine → N-(3-chloro-4-fluorophenyl)-7-{(2E)-4-[isopropyl(methyl)amino]but-2-enoyl}-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine

HRID 1887415Notes

Reaction equation

HRID 1887415 reaction equation
Br[CH2:2][CH:3]=[CH:4][C:5]([N:7]1[CH2:19][C:18]2[S:17][C:16]3[N:15]=[CH:14][N:13]=[C:12]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=4)[C:11]=3[C:10]=2[CH2:9][CH2:8]1)=[O:6].[CH:29]([NH:32][CH3:33])([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.CO.ClCCl>ClCCl.CN(C=O)C.CC#N.O>[Cl:28][C:23]1[CH:22]=[C:21]([NH:20][C:12]2[C:11]3[C:10]4[CH2:9][CH2:8][N:7]([C:5](=[O:6])/[CH:4]=[CH:3]/[CH2:2][N:32]([CH:29]([CH3:31])[CH3:30])[CH3:33])[CH2:19][C:18]=4[S:17][C:16]=3[N:15]=[CH:14][N:13]=2)[CH:26]=[CH:25][C:24]=1[F:27]

Participants

9

Reactant 4

HCID 78485N-MethylisopropylamineHCID 81531DiisopropylethylamineHCID 21226129Dichloromethane methanolHCID 668497424-Bromo-1-[4-(3-chloro-4-fluoro-phenylamino)-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluoren-7-yl]-but-2-en-1-one

Product 1

HCID 24748609N-(3-chloro-4-fluorophenyl)-7-{(2E)-4-[isopropyl(methyl)amino]but-2-enoyl}-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amineYield 19%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-bath cooled solution of 4-Bromo-1-[4-(3-chloro-4-fluoro-phenylamino)-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluoren-7-yl]-but-2-en-1-one (0.14 g, 0.291 mmol) in dichloromethane (4.0 ml) was added isopropylmethylamine (0.121 ml, 1.16 m mol) followed by the addition of DIEA (0.056 ml, 0.32 mmol). The resulting mixture was stirred at RT overnight. TLC (10% MeOH/Dichloromethane) indicates no starting material present. The crude mixture was rotavapped to dryness, dissolved in DMF & subjected to HPLC conditions [H2O (containing 0.1% NH4OH)-MeCN] to give the desired product (26 mg, 19%). 1H-NMR (DMSO-d6) δ 8.46 (m, 1H), 8.39 (s, 1H), 7.88 (m, 1H), 7.62 (m, 1H), 7.42 (t, 1H), 6.67 (m, 1H), 3.94 (m, 2H), 3.87 (m, 4H), 2.75 (m, 2H), 2.11 (s, 3H), 0.96 (d, 6H); LCMS RT=2.53 min, [M+H]+=474.1.

Sources & evidence

ORD record
ord-219c04f39c604b7f87ffc0391e54598b
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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