O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → (S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-{[(tetrahydropyran-4-ylmethyl)-carbamoyl]-methyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963065Notes

Reaction equation

HRID 1963065 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[N:32]3[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]3)=[C:26]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:25]=2[CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=2[CH3:47])=[O:23])[CH2:18][C@@H:17]1[CH2:48][C:49](O)=[O:50])=[O:15])([CH3:12])([CH3:11])[CH3:10].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([C:24]2[N:32]3[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]3)=[C:26]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:25]=2[CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=2[CH3:47])=[O:23])[CH2:18][C@@H:17]1[CH2:48][C:49](=[O:50])[NH:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1)=[O:15])([CH3:11])([CH3:12])[CH3:10]

Participants

5

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27732104-AminomethyltetrahydropyranHCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid

Product 1

HCID 70663881(S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-{[(tetrahydropyran-4-ylmethyl)-carbamoyl]-methyl}-piperazine-1-carboxylic acid tert-butyl esterYield 63.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred, ice-cold solution of 4-aminomethyl-tetrahydropyran (0.047 g, 0.40 mmol), EDIA (0.19 ml, 1.08 mmol) and the compound of step 2 (0.190 g, 0.27 mmol) was added TBTU (0.259 g, 0.81 mmol) in small portions. The solution was stirred at room temperature for 18 h. Then water (8 ml) was added and the mixture was extracted 3 times with EA. The combined organic phases were washed with 1 N hydrochloric acid, water, a saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0, then 50:50) to give 0.117 g of the title compound as an orange gum.

Workup

  1. extractionthe mixture was extracted 3 times with EA
  2. washThe combined organic phases were washed with 1 N hydrochloric acid, water
  3. dry with materiala saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0

Sources & evidence

ORD record
ord-1b68f16768c74f6b8102b3113961876c
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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