Diisopropylethylamine → (1-methyl-1H-pyrrol-2-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)piperidin-1-yl]methanone

HRID 1805987Notes

Reaction equation

HRID 1805987 reaction equation
C1(N2CCN([C:13]3[N:14]=[C:15]([NH:22][C@H:23]4[CH2:27][CH2:26][CH2:25][C@@H:24]4[NH:28][C:29](=[O:35])OC(C)(C)C)[C:16]4[S:21][CH2:20][CH2:19][C:17]=4[N:18]=3)CC2)C=CC=CC=1.[CH:36]([N:39]([CH:42]([CH3:44])C)[CH2:40]C)([CH3:38])C.Cl.[Cl:46]C1N=C(NC2CCCNC2)C2SCCC=2N=1>CS(C)=O>[CH3:40][N:39]1[CH:36]=[CH:38][CH:44]=[C:42]1[C:29]([N:28]1[CH2:25][CH2:26][CH2:27][CH:23]([NH:22][C:15]2[C:16]3[S:21][CH2:20][CH2:19][C:17]=3[N:18]=[C:13]([Cl:46])[N:14]=2)[CH2:24]1)=[O:35]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 86616269tert-butyl {(1S,2S)-2-[2-(4-phenylpiperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino]cyclopentyl}carbamateHCID 86616275(2-Chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride

Product 1

HCID 86616276(1-methyl-1H-pyrrol-2-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)piperidin-1-yl]methanoneYield 85.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

0.462 g (3.7 mmol) of 1-methyl-1H-pyrrol-2-carboxylic acid (VII), 1.4 g (9.7 mmol) of O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU), and 0.640 mL (3.7 mmol) of diisopropylethylamine are placed in 10 mL of dimethylsulfoxide, then stirred for 0.1 hours at ambient temperature. 0.814 g (3.0 mmol) of (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride (VI) and 3.7 mmol of diisopropylethylamine are added, then the mixture is stirred for 16 hours at ambient temperature. Then the reaction mixture is suction filtered through Alox, and the mother liquor is concentrated by evaporation. The residue is combined with 1 N sodium hydroxide solution and extracted with dichloromethane. The organic phase is separated off using a phase separator and evaporated to dryness. The crude product is purified by chromatography through a Biotage silica gel cartridge 40s with petroleum ether/ethyl acetate 1:1. 0.970 g of product VIII (85%) is obtained.

Workup

  1. stirringthe mixture is stirred for 16 hours at ambient temperature
  2. filtrationfiltered through Alox
  3. concentrationthe mother liquor is concentrated by evaporation
  4. extractionextracted with dichloromethane
  5. customThe organic phase is separated off
  6. customevaporated to dryness
  7. customThe crude product is purified by chromatography through a Biotage silica gel cartridge 40s with petroleum ether/ethyl acetate 1:1

Sources & evidence

ORD record
ord-1c28d34b66934c12acbe27da61f1307d
Source dataset
uspto-grants-2013_01
Patent number
US08354531B2

Reaction notes

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