2-Methylpropan-2-olate → HCID 89647581, compound

HRID 2281015Notes

Reaction equation

HRID 2281015 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([C:12]#[N:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:36])([F:35])[F:34])[CH:27]=2)[CH:23]([NH2:37])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Na].CC([O-])(C)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:34])([F:35])[F:36])[CH:27]=2)[CH:23]([NH:37][C:2]2[CH:11]=[CH:10][C:9]([C:12]#[N:13])=[C:8]3[C:3]=2[CH:4]=[CH:5][CH:6]=[N:7]3)[CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 5

HCID 45749132-Methylpropan-2-olateHCID 5360545SodiumHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 112763365-Bromoquinoline-8-carbonitrileHCID 66715044HCID 66715044, compound

Product 1

HCID 89647581HCID 89647581, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A reaction mixture of 5-Bromo-quinoline-8-carbonitrile (200.00 mg; 0.86 mmol; 1.00 eq), (3-amino-4-(3-trifluoromethoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.41 ml; 1.03 mmol; 1.20 eq.) (trans_racemic), sodium; 2-methyl-propan-2-olate (181.43 mg; 1.89 mmol; 2.20 eq.), and dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (122.73 mg; 0.26 mmol; 0.30 eq.) in toluene (5 ml) in microwave tube was degas, followed by adding Pd2(dba)3 (74.02 mg; 0.13 mmol; 0.15 eq.). The resulting mixture was stirred for 10 min at RT, placed in microwave at 100° C. for 20 min. The reaction mixture was concentrated and re-dissolved in DMSO, purified by prep HPLC (Basic condition, 70-75% acetonitrile in water) to give 3-(8-cyano-quinolin-5-ylamino)-4-(3-trifluoromethoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (trans_racemic) (150 mg, 35%).

Workup

  1. waitplaced in microwave at 100° C. for 20 min
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionre-dissolved in DMSO
  4. custompurified by prep HPLC (Basic condition, 70-75% acetonitrile in water)

Sources & evidence

ORD record
ord-539c41961639403d94c78a2559f0be45
Source dataset
uspto-grants-2015_09
Patent number
US09139568B2

Reaction notes

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