1-Aminocyclobutanecarboxylic acid → (E)-3-[2-(1-aminocyclobutyl)-1-methyl-1H-benzoimidazol-5-yl]acrylic acid methyl ester

HRID 1360629Notes

Reaction equation

HRID 1360629 reaction equation
[CH3:1][O:2][C:3](=[O:15])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([NH:12][CH3:13])=[C:8]([NH2:14])[CH:7]=1.[NH2:16][C:17]1([C:21](O)=O)[CH2:20][CH2:19][CH2:18]1>C(Cl)Cl.Cl.NC1(C(Cl)=O)CCC1.C(O)(=O)C.C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3](=[O:15])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]2[N:12]([CH3:13])[C:21]([C:17]3([NH2:16])[CH2:18][CH2:19][CH2:20]3)=[N:14][C:8]=2[CH:7]=1

Participants

7

Reactant 2

HCID 896431-Aminocyclobutanecarboxylic acidHCID 58866234(E)-3-(3-amino-4-methylaminophenyl)acrylic acid methyl ester

Product 1

HCID 58866235(E)-3-[2-(1-aminocyclobutyl)-1-methyl-1H-benzoimidazol-5-yl]acrylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolventHCID 21105264Cyclobutanecarbonyl chloride, 1-amino-, hydrochlorideSolvent

Procedure

(E)-3-(3-Amino-4-methylaminophenyl)acrylic acid methyl ester 2-4 from Example 2 (40 mg, 0.194 mmol) was suspended in CH2Cl2 (3 mL) and 1-aminocyclobutanecarboxylic acid chloride hydrochloride, prepared from 1-aminocyclobutanecarboxylic acid following an adaptation of the procedure described by E. S. Uffelman et al. (Org. Lett. 1999, 1, 1157), (31 mg, 0.18 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours and then concentrated to obtain a white solid. The solid was then dissolved in acetic acid (5 mL) and heated to 60° C. for 20 hours. The reaction crude was diluted with aqueous saturated NaHCO3, extracted with CH2Cl2 (2×50 mL) and brine, the organic layer was dried over anhydrous MgSO4 and the solvent was removed under reduced pressure to give (E)-3-[2-(1-aminocyclobutyl)-1-methyl-1H-benzoimidazol-5-yl]acrylic acid methyl ester 3-1 as a light brown foam (53 mg).

Workup

  1. additionUffelman et al. (Org. Lett. 1999, 1, 1157), (31 mg, 0.18 mmol) was added
  2. concentrationconcentrated
  3. customto obtain a white solid
  4. temperatureheated to 60° C. for 20 hours
  5. customThe reaction crude
  6. extractionextracted with CH2Cl2 (2×50 mL) and brine
  7. dry with materialthe organic layer was dried over anhydrous MgSO4
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-82aa502f6a3c490997c19d0e89b00239
Source dataset
uspto-grants-2011_02
Patent number
US07879851B2

Reaction notes

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