N,N'-Dimethylethylenediamine → HCID 67298694, compound

HRID 1008993Notes

Reaction equation

HRID 1008993 reaction equation
[F:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8]1[C:9]2[S:28][C:27]([C:29]([O:31][CH3:32])=[O:30])=[CH:26][C:10]=2[N:11]([CH2:21][C:22](OC)=[O:23])[C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]=O.C[NH:34][CH2:35][CH2:36][NH:37][CH3:38].[BH3-][C:40]#N.[Na+].CCOC(C)=O>CO>[CH3:40][N:37]([CH3:38])[CH2:36][CH2:35][N:34]1[CH2:19][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12]2=[C:8]([C@H:3]3[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]3[F:1])[C:9]3[S:28][C:27]([C:29]([O:31][CH3:32])=[O:30])=[CH:26][C:10]=3[N:11]2[CH2:21][C:22]1=[O:23]

Participants

6

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 8857Ethyl AcetateHCID 5003444Sodium cyanoborohydrideHCID 86629784methyl 6-(2-fluorocyclohexyl)-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 67298694HCID 67298694, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution (0.1 M) of methyl 6-(2-fluorocyclohexyl)-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate and dimethylethylenediamine (1.5 eq.) in MeOH was stirred at RT for 3 h, then NaCNBH3 (excess) was added and the mixture was stirred for 3 days; evaporation to dryness gave a residue that was taken into EtOAc and washed with sat. NaHCO3-solution and brine, dried and concentrated i. vac. to obtain methyl 6-[2-(dimethylamino)ethyl]-13-[(1R,2S)-2-fluorocyclohexyl]-7-oxo-5,6,7,8-tetrahydrothieno[2′,3′:4,5]pyrrolo[2,1-a][2,5]benzodiazocine-11-carboxylate that was used without further purification. The latter was dissolved in dry THF (0.1M) and treated with 2M borane dimethylsulfide complex in THF (excess), and the mixture was stirred overnight at RT. 1.25M HCl in MeOH was added dropwise, the flask was opened and the mixture was stirred for 3 h at 85° C. Evaporation to dryness gave a residue that was hydrolised with 1M aq. KOH (3 eq.) in dioxane (85° C., 2 h); after quenching with 6M aq. HCl and removal of all volatiles the title compound was isolated by RP-HPLC. Yield: 60%. 1H-NMR (400 MHz, DMSO-d6, 300K, δ) 8.04 (d, 1H, J 2.2) 7.85-7.46 (m, 4H), 4.74-4.69 (m, 1H), 4.86-4.45 (m, 1H), 4.40 (bt, 1H, J 12.5), 3.74-3.42 (m, 8H), 2.88 (s, 3H), 2.87 (s, 3H), 2.74-2.61 (m, 1H), 2.26-1.03 (m, 8H); MS (ES+) m/z 470 (M+H)+.

Workup

  1. customevaporation to dryness
  2. customgave a residue that
  3. washwashed with sat. NaHCO3-solution and brine
  4. customdried
  5. concentrationconcentrated i

Sources & evidence

ORD record
ord-e8e6acf46db54017b6050ff1845ee961
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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