Citric Acid → HCID 67974867, compound

HRID 1502287Notes

Reaction equation

HRID 1502287 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]([CH3:22])([O-:21])[CH3:20].[Na+].C1(C)C=CC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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.C(Cl)(Cl)Cl.[Pd].[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[C:19]([O:21][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1)([CH3:22])([CH3:20])[CH3:18]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974867HCID 67974867, compoundYield 5.2%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalyst

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (70.6 mg, 0.242 mmol), sodium tert-butoxide (36.0 mg, 0.374 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (13.0 mg, 0.0126 mmol), and Q-Phos (19.3 mg, 0.0272 mmol) in toluene (1.0 mL, 9.4 mmol) was subjected to microwave irradiation at 120° C. for 30 minutes. The reaction mixture was neutralized with 10% aqueous citric acid and extracted with dichloromethane. The organic extract was dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 3.6 mg (5.2%) of N-(7-tert-butoxyisoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.371, M+H=285.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.06 (s, 1H), 8.40 (s, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.60 (d, J=2.2 Hz, 1H), 7.35 (dd, J=8.9, 2.4 Hz, 1H), 2.12-1.97 (m, 1H), 1.39 (s, 9H), 0.91-0.75 (m, 4H).

Workup

  1. customirradiation at 120° C. for 30 minutes
  2. extractionextracted with dichloromethane
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-c04fa385b24c4c7ca10b3968ca6f0754
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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