Formic Acid → {(S)-3-[(6-Chloro-benzooxazol-2-ylamino)-methyl]-pyrrolidin-1-yl}-(2,6-dimethoxy-phenyl)-methanone

HRID 403335

Reaction equation

HRID 403335 reaction equation
Cl.[Cl:2][C:3]1[CH:18]=[CH:17][C:6]2[N:7]=[C:8]([NH:10][CH2:11][C@@H:12]3[CH2:16][CH2:15][NH:14][CH2:13]3)[O:9][C:5]=2[CH:4]=1.[CH3:19][O:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[C:22]=1[C:23](O)=[O:24].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)=O>CN(C=O)C.CCN(C(C)C)C(C)C>[Cl:2][C:3]1[CH:18]=[CH:17][C:6]2[N:7]=[C:8]([NH:10][CH2:11][C@@H:12]3[CH2:16][CH2:15][N:14]([C:23]([C:22]4[C:26]([O:30][CH3:31])=[CH:27][CH:28]=[CH:29][C:21]=4[O:20][CH3:19])=[O:24])[CH2:13]3)[O:9][C:5]=2[CH:4]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 151092,6-Dimethoxybenzoic AcidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 131728778(6-Chloro-benzooxazol-2-yl)-(R)-1-pyrrolidin-3-ylmethyl-amine, hydrochloride2×

Product 1

HCID 44628353{(S)-3-[(6-Chloro-benzooxazol-2-ylamino)-methyl]-pyrrolidin-1-yl}-(2,6-dimethoxy-phenyl)-methanoneYield 38.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A mixture of 146.3 mg (0.45 mmol) (6-chloro-benzooxazol-2-yl)-(R)-1-pyrrolidin-3-ylmethyl-amine, hydrochloride (intermediate 1), 106.7 mg (0.586 mmol) 2,6-dimethoxy-benzoic acid (commercially available) and 206.9 mg (0.64 mmol) TBTU in 4 mL DMF and 0.3 mL DIPEA was shaken at room temperature over night. The mixture was acidified with formic acid and subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid. The product containing fractions were evaporated to yield 72 mg (38%) of the title compound. MS (m/e): 416.2 (MH+).

Workup

  1. customsubjected to purification by preparative HPLC on reversed phase
  2. washeluting with a gradient
  3. customformed from acetonitrile, water and formic acid
  4. additionThe product containing fractions
  5. customwere evaporated

Sources & evidence

ORD record
ord-963c8292b1d241da95f68241cb4e808e
Source dataset
uspto-grants-2014_06
Patent number
US08748430B2

Linked notes

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