1,1'-Carbonyldiimidazole → (4-Dimethylamino-piperidin-1-yl)-(4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone

HRID 1947020Notes

Reaction equation

HRID 1947020 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:13][S:14]([CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[CH:24][N:25]2[C:30]1[CH:35]=[CH:34][N:33]=[C:32]([NH:36][CH:37]2[CH2:42][CH2:41][CH:40]([C:43]([OH:45])=O)[CH2:39][CH2:38]2)[N:31]=1)(=[O:16])=[O:15].[CH3:46][N:47]([CH:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1)[CH3:48]>CN(C=O)C>[CH3:46][N:47]([CH3:48])[CH:49]1[CH2:54][CH2:53][N:52]([C:43]([CH:40]2[CH2:39][CH2:38][CH:37]([NH:36][C:32]3[N:31]=[C:30]([N:25]4[C:26]5[C:22](=[C:21]([O:20][CH2:19][CH2:18][CH2:17][S:14]([CH3:13])(=[O:15])=[O:16])[CH:29]=[CH:28][CH:27]=5)[CH:23]=[CH:24]4)[CH:35]=[CH:34][N:33]=3)[CH2:42][CH2:41]2)=[O:45])[CH2:51][CH2:50]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 417391N,N-Dimethylpiperidin-4-amineHCID 580170794-{4-[4-(3-Methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid

Product 1

HCID 59743556(4-Dimethylamino-piperidin-1-yl)-(4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

CDI (7.13 g, 44.0 mmol) was added to a mixture of 4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid (16.00 g, 33.86 mmol) in dry DMF (100 mL) heated to 40° C. under N2. After stirring for 10 min, 100 mL of DMF was added, heated to 40° C., and stirred for an additional 40 min. N,N-dimethyl-piperidin-4-ylamine (5.00 g, 38.9 mmol) was added and allowed to stir overnight at RT. The reaction mixture was concentrated in vacuo, the residue diluted with EtOAc and washed with cold H2O (4×), 5% NaOH aqueous solution (4×), H2O and brine. The organic layer was dried and the remaining solvent removed in vacuo. The product, (4-dimethylamino-piperidin-1-yl)-(4-{4-[4-(3-methane-sulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone (Compound 275), was crystallized from EtOH/H2O as a white solid (11.9 g, 60.3%). MS M+1 (583), mp 182.4-183° C.

Workup

  1. temperatureheated to 40° C.
  2. stirringstirred for an additional 40 min
  3. stirringto stir overnight at RT
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additionthe residue diluted with EtOAc
  6. washwashed with cold H2O (4×), 5% NaOH aqueous solution (4×), H2O and brine
  7. customThe organic layer was dried
  8. customthe remaining solvent removed in vacuo
  9. customThe product, (4-dimethylamino-piperidin-1-yl)-(4-{4-[4-(3-methane-sulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone (Compound 275), was crystallized from EtOH/H2O as a white solid (11.9 g, 60.3%)

Sources & evidence

ORD record
ord-0c5f20b1a6204fd7bd6f31df5f23e116
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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