Water → 4-{4-[4-(1,1-Dioxo-tetrahydro-1lambda*6*-thiophen-3-ylmethoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid ethyl ester

HRID 237432Notes

Reaction equation

HRID 237432 reaction equation
[O:1]=[S:2]1(=[O:29])[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][N:13]3[C:18]2[CH:23]=[CH:22][N:21]=[C:20](S(CCC)=O)[N:19]=2)[CH2:3]1.Cl.[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][CH:39]([NH2:42])[CH2:38][CH2:37]1)=[O:35])[CH3:32].C(N(C(C)C)CC)(C)C.O>CN1C(=O)CCC1>[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][CH:39]([NH:42][C:20]2[N:19]=[C:18]([N:13]3[C:14]4[C:10](=[C:9]([O:8][CH2:7][CH:4]5[CH2:5][CH2:6][S:2](=[O:29])(=[O:1])[CH2:3]5)[CH:17]=[CH:16][CH:15]=4)[CH:11]=[CH:12]3)[CH:23]=[CH:22][N:21]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 11586508trans-Ethyl 4-aminocyclohexanecarboxylate hydrochlorideHCID 585421604-(1,1-dioxo-tetrahydro-1lambda*6*-thiophen-3-ylmethoxy)-1-[2-(propane-1-sulfinyl)-pyrimidin-4-yl]-1H-indole

Product 1

HCID 585421644-{4-[4-(1,1-Dioxo-tetrahydro-1lambda*6*-thiophen-3-ylmethoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid ethyl esterYield 75.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(1,1-dioxo-tetrahydro-1lambda*6*-thiophen-3-ylmethoxy)-1-[2-(propane-1-sulfinyl)-pyrimidin-4-yl]-1H-indole 1.2 g) and 4-amino-cyclohexanecarboxylic acid ethyl ester HCl salt (1.12 g) in NMP (5 mL) was added diisopropylethylamine (1.4 mL). The mixture was heated to 80° C. for 18 hours, then cooled and poured into 75 mL water. The mixture was extracted with methylene chloride, and the combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (60% EtOAc in hexanes) to give 1.069 g of 4-{4-[4-(1,1-dioxo-tetrahydro-1lambda*6*-thiophen-3-ylmethoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid ethyl ester.

Workup

  1. temperaturecooled
  2. extractionThe mixture was extracted with methylene chloride
  3. dry with materialthe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-223da95480584a8ab75e90534097b2e8
Source dataset
uspto-grants-2014_02
Patent number
US08642601B2

Reaction notes

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