Diisopropylethylamine → ethyl (R) 3-[4-(2-{4-[(2,3-dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl}-acetylamino)-phenyl]-butyrate

HRID 1167809Notes

Reaction equation

HRID 1167809 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH3:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[N:16]1([C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35](O)=[O:36])=[CH:30][C:29]=2[O:38][CH3:39])=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.O>[N:16]1([C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C@H:8]([CH3:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=3)=[O:36])=[CH:30][C:29]=2[O:38][CH3:39])=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 229942374-[(2,3-Dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl-acetic acidHCID 53963459HCID 53963459, compound

Product 1

HCID 86585371ethyl (R) 3-[4-(2-{4-[(2,3-dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl}-acetylamino)-phenyl]-butyrateYield 86.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl (R) 3-(4-aminophenyl)butyrate (790 mg), 4-[(2,3-dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl-acetic acid (1.24 g, Reference Example 5) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.45 g) in dimethylformamide (20 mL) was treated in one portion with diisopropylethylamine (1.4 mL). The resulting mixture was stirred at room temperature for 2 hours then poured into water (100 mL) and then extracted three times with ethyl acetate (50 mL). The combined extracts were washed with hydrochloric acid (0.5M), then with sodium hydrogen carbonate solution, then dried and then evaporated. The residue was triturated with a mixture of ethyl acetate and petrol to give the title compound (1.7 g) as a pink/orange powder. HPLC: RT=18.9 minutes (86% by ELS).

Workup

  1. extractionextracted three times with ethyl acetate (50 mL)
  2. washThe combined extracts were washed with hydrochloric acid (0.5M)
  3. dry with materialwith sodium hydrogen carbonate solution, then dried
  4. customevaporated
  5. customThe residue was triturated with a mixture of ethyl acetate and petrol

Sources & evidence

ORD record
ord-82ed5716f1d54d2993bb5518995d74e8
Source dataset
uspto-grants-2003_09
Patent number
US06620832B2

Reaction notes

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