Diisopropylethylamine → (R)-1-(4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarbonyl)-piperidine-3-carboxylic acid ethyl ester

HRID 237434

Reaction equation

HRID 237434 reaction equation
[CH3:1][S:2]([CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][N:13]2[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]2[CH2:30][CH2:29][CH:28]([C:31]([O-])=[O:32])[CH2:27][CH2:26]2)[N:19]=1)(=[O:4])=[O:3].[Na+].[CH2:35]([O:37][C:38]([C@@H:40]1[CH2:45][CH2:44][CH2:43][NH:42][CH2:41]1)=[O:39])[CH3:36].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>O.CN(C=O)C>[CH2:35]([O:37][C:38]([C@@H:40]1[CH2:45][CH2:44][CH2:43][N:42]([C:31]([CH:28]2[CH2:27][CH2:26][CH:25]([NH:24][C:20]3[N:19]=[C:18]([N:13]4[C:14]5[C:10](=[C:9]([O:8][CH2:7][CH2:6][CH2:5][S:2]([CH3:1])(=[O:3])=[O:4])[CH:17]=[CH:16][CH:15]=5)[CH:11]=[CH:12]4)[CH:23]=[CH:22][N:21]=3)[CH2:30][CH2:29]2)=[O:32])[CH2:41]1)=[O:39])[CH3:36]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 86659980Sodium 4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylate

Product 1

HCID 54754660(R)-1-(4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarbonyl)-piperidine-3-carboxylic acid ethyl esterYield 8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium 4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylate (0.4 g), (R)-piperidine-3-carboxylic acid ethyl ester (0.165 g), BOP (0.537 g) and DIPEA (0.56 mL) were added to DMF (3 mL), and the mixture was stirred at room temperature overnight. The mixture was diluted with water and the resulting precipitate was collected by filtration, washed with water, dried under reduced pressure, and purified by flash chromatography (DCM/MeOH) to give 39.6 mg of (R)-1-(4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarbonyl)-piperidine-3-carboxylic acid ethyl ester, MP=175.0-177.0° C.

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. washwashed with water
  3. customdried under reduced pressure
  4. custompurified by flash chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-e0ad66e339c2487e8f8fad8c61234c2f
Source dataset
uspto-grants-2014_02
Patent number
US08642601B2

Linked notes

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