Diisopropylethylamine → (3RS)-3-{5-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-pyrid-2-yl}-butyric acid ethyl ester

HRID 49700Notes

Reaction equation

HRID 49700 reaction equation
F[C:2](F)(F)[C:3](O)=O.[C:8]1([CH3:40])[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1N[C:17]2[CH:23]=[C:22]([CH2:24][C:25]([NH:27][C:28]3[CH:29]=[CH:30][C:31]([CH:34]([CH3:39])[CH2:35][C:36]([OH:38])=[O:37])=[N:32][CH:33]=3)=[O:26])[CH:21]=[CH:20][C:18]=2[N:19]=1.F[P-](F)(F)(F)(F)F.N1([O:57]C(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.NC1C=CC(C(C)CC(OCC)=O)=NC=1>CN(C)C=O>[CH2:2]([O:38][C:36](=[O:37])[CH2:35][CH:34]([C:31]1[CH:30]=[CH:29][C:28]([NH:27][C:25](=[O:26])[CH2:24][C:22]2[CH:21]=[CH:20][C:18]3[N:19]=[C:15]([NH:14][C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[CH3:40])[O:57][C:17]=3[CH:23]=2)=[CH:33][N:32]=1)[CH3:39])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9829176(3RS)-3-{5-[2-(2-o-Tolylamino-3H-benzimidazol-5-yl)-acetylamino]-pyridin-2-yl}-butyric acid trifluoroacetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 17946645ethyl (3RS)-3-(5-aminopyrid-2-yl)butyrate

Product 1

HCID 9890975(3RS)-3-{5-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-pyrid-2-yl}-butyric acid ethyl esterYield 140.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of 2-o-tolylamino-benzoxazol-6-acetic acid (0.42 g, Reference Example 2) in dimethylformamide (15 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.57 g), then with diisopropylethylamine (0.4 g) and then with a solution of ethyl (3RS)-3-(5-aminopyrid-2-yl)butyrate (0.3 g, Reference Example 5) in dimethylformamide (5 mL). The mixture was stirred at room temperature for 5 hours then left to stand over night and then evaporated to low bulk. The residue was partitioned between water and ethyl acetate. The organic phase was washed with dilute acetic acid, then with water, then with aqueous bicarbonate solution (5%), then with water, then with brine, then dried and then evaporated. The residue was subjected to flash chromatography on silica eluting with ethyl acetate to give the title compound (0.5 g) as a colourless glass. TLC: RF=0.36 (eluting with ethyl acetate). MS: 473 (MH+).

Workup

  1. waitthen left
  2. waitto stand over night
  3. customevaporated to low bulk
  4. customThe residue was partitioned between water and ethyl acetate
  5. washThe organic phase was washed with dilute acetic acid
  6. dry with materialwith water, then with aqueous bicarbonate solution (5%), then with water, then with brine, then dried
  7. customevaporated

Sources & evidence

ORD record
ord-ab39d4a2592841388c2555f65dd8ac8e
Source dataset
uspto-grants-2004_03
Patent number
US06706738B2

Reaction notes

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