Potassium Phosphate, Tribasic → methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid

HRID 56364Notes

Reaction equation

HRID 56364 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C@@H:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[N:6]=[CH:5]2.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)[C:31]([OH:33])=[O:32].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:55]1.O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:55][C:29]1[C:28]([O:27][CH3:26])=[C:36]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([NH:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[NH:18][C:19]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:25])[N:6]=[CH:5]3)[CH:35]=[CH:34][C:30]=1[C:31]([OH:33])=[O:32]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 218864351,4-Dioxane--water (1/1)HCID 467397043-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 118043383tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate

Product 1

HCID 118036162methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acidYield 96%

Reagents, catalysts & solvents 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate (100 mg, 0.25 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (82 mg, 0.29 mmol), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (9 mg, 0.01 mmol) and potassium phosphate (157 mg, 0.74 mmol) in 1,4-dioxane/water (2.5 mL/0.25 mL) was degassed with nitrogen for 5 min and stirred at 100° C. for 30 min under microwave. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated ammonium chloride solution and dried with sodium sulfate. The residue was purified by silica gel column chromatography to afford methyl 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid (114 mg, 96%). MS (ES+) C26H30N4O5 requires: 478, found: 479 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washwashed with saturated ammonium chloride solution
  5. dry with materialdried with sodium sulfate
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1391f68d032143e08655acb2a36661e3
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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