Diisopropylethylamine → 4-Cyclobutylmethoxy-1H-indole-2-carboxylic acid {4-hydroxy-4-[2-((3S,4S)-4-hydroxy-3-methyl-piperidin-1-yl)-ethyl]-cyclohexyl}-amide

HRID 1804795Notes

Reaction equation

HRID 1804795 reaction equation
[CH:1]1([CH2:5][O:6][C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH:9]=[C:10]([C:16]([OH:18])=O)[NH:11]3)[CH2:4][CH2:3][CH2:2]1.[NH2:19][CH:20]1[CH2:25][CH2:24][C:23]([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][C@H:32]([OH:35])[C@@H:31]([CH3:36])[CH2:30]2)([OH:26])[CH2:22][CH2:21]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[OH:26][C:23]1([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][C@H:32]([OH:35])[C@@H:31]([CH3:36])[CH2:30]2)[CH2:24][CH2:25][CH:20]([NH:19][C:16]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[C:7]([O:6][CH2:5][CH:1]2[CH2:2][CH2:3][CH2:4]2)[CH:15]=[CH:14][CH:13]=3)=[O:18])[CH2:21][CH2:22]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59152645HCID 59152645, compoundHCID 591526824-Cyclobutylmethoxy-1H-indole-2-carboxylic acid

Product 1

HCID 591526544-Cyclobutylmethoxy-1H-indole-2-carboxylic acid {4-hydroxy-4-[2-((3S,4S)-4-hydroxy-3-methyl-piperidin-1-yl)-ethyl]-cyclohexyl}-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-cyclobutylmethoxy-1H-indole-2-carboxylic acid (16a) (140 mg, 0.383 mmol), (3S,4S)-1-[2-(4-amino-1-hydroxy-cyclohexyl)-ethyl]-3-methyl-piperidin-4-ol (14) (103 mg, 0.421 mmol) and DIEA (0.263 ml, 1.532 mmol) in 5 ml of DMF is treated with solid TBTU (139 mg, 0.421 mmol). The mixture is stirred for 2 h at rt and then evaporated. The crude residue is dissolved in EtOAc and extracted with 1M-HCl. The aqueous layer is separated, its pH adjusted to 14 and extracted 3-times with DCM. The organic layers are dried over sodium sulphate and evaporated. The crude product is then purified by chromatography on silicagel using methanol and DCM (saturated with ammonia) from 1:99 to 5:95.

Workup

  1. customevaporated
  2. dissolutionThe crude residue is dissolved in EtOAc
  3. extractionextracted with 1M-HCl
  4. customThe aqueous layer is separated
  5. extractionextracted 3-times with DCM
  6. dry with materialThe organic layers are dried over sodium sulphate
  7. customevaporated
  8. customThe crude product is then purified by chromatography on silicagel

Sources & evidence

ORD record
ord-a91f42adc7b5434cbdd9d13d74296632
Source dataset
uspto-grants-2013_01
Patent number
US08354431B2

Reaction notes

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