Nitrogen → HCID 11180883, compound

HRID 2103369Notes

Reaction equation

HRID 2103369 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:36])[CH2:13][CH2:12][CH:11]([NH:14][C@H:15]3[CH2:19][CH2:18][N:17]([C:20](=[O:35])[CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=4)[CH2:16]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O)=[O:38].N#N.ClCCl>CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+].Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:36])[CH2:13][CH2:12][CH:11]([NH:14][C@H:15]3[CH2:19][CH2:18][N:17]([C:20](=[O:35])[CH2:21][NH:22][C:23](=[O:34])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:31])[F:33])[CH:25]=4)[CH2:16]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1)=[O:38]

Participants

8

Reactant 4

HCID 947Nitrogen2×HCID 6344DichloromethaneHCID 2921892-Formylphenylboronic acidHCID 67011693HCID 67011693, compound

Product 1

HCID 11180883HCID 11180883, compoundYield 74.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A solution of N-[2-((3S)-3-[4-(5-bromopyridin-2-yl)-4-hydroxycyclohexyl]aminopyrrolidin-1-yl)-2-oxoethyl]-3-(trifluoromethyl)benzamide (30.0 mg, 0.0527 mmol) and (2-formylphenyl)boronic acid (8.6 mg, 0.052 mmol) in DMF (0.60 mL) and aqueous sodium carbonate (2M, 0.198 mL) was degassed with N2 for 5 minutes. Then [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (2.2 mg, 0.0026 mmol) was added in under N2 flush. The reaction mixture was degassed with N2 for another 5 minutes and then the tube was sealed. The reaction mixture was heated under microwave at 130° C. for 5 minutes. After cooling down, the reaction mixture was filtered through a short pad of silica gel and washed with CH3CN. The resulting solution was acidified with TFA to pH 1˜2, then was subjected to purification on Prep-HPLC. The appropriate fractions were lypholized to give the product (23 mg, 53%) as a white powder. MS: (M+H)+ 595.

Workup

  1. customflush
  2. customThe reaction mixture was degassed with N2 for another 5 minutes
  3. customthe tube was sealed
  4. temperatureAfter cooling down
  5. filtrationthe reaction mixture was filtered through a short pad of silica gel
  6. washwashed with CH3CN
  7. customwas subjected to purification on Prep-HPLC

Sources & evidence

ORD record
ord-43ba7b3e50b348e484de04c987acce39
Source dataset
uspto-grants-2009_08
Patent number
US07576089B2

Reaction notes

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