Diisopropylethylamine → (S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate

HRID 2036574Notes

Reaction equation

HRID 2036574 reaction equation
[NH2:1][C:2]1[C:3]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[NH:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:17]([C:19](O)=[O:20])[CH3:18].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C2=CC=CC=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH:13]1([NH:12][C:3]2[C:4]([C:5](=[O:6])[NH:7][CH3:8])=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:19](=[O:20])[C@@H:17]([NH:16][C:22](=[O:23])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH3:18])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 2724699PyBOPHCID 584592993-amino-2-(cyclopropylamino)-N-methylbenzamide

Product 1

HCID 58459271(S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-amino-2-(cyclopropylamino)-N-methylbenzamide (1.31 g, 6.38 mmol) in DMF (3 mL) was added Boc-L-Ala-OH (1.21 g, 6.38 mmol), 1,1′-dimethyltriethylamine (2.22 mL, 12.8 mmol) and (1H-benzo[d][1,2,3]triazol-1-yloxy)tripyrrolidin-1-ylphosphonium hexafluorophosphate(V) (3.99 g, 7.66 mmol) the resulting mixture was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. After being concentrated under reduced pressure, the residue was purified by column chromatography on a silica gel column using EtOAc:DCM (1:1) as eluent to give (S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate: 1H NMR (400 MHz, CDCl3) δ 8.56 (br, 1H), 8.14 (d, J=8 Hz, 1H), 7.18 (d, J=8 Hz, 1H), 6.99 (dd, J=8, 8 Hz, 1H), 6.24 (br, 1H), 6.01 (br, 1H), 4.38 (br, 1H), 3.00 (d, J=4 Hz, 3H), 2.58 (br, 1H), 1.60 (s, 3H), 1.48 (s, 9H), 0.64-0.59 (m, 2H), 0.54-0.49 (m, 2H); LC-MS (ESI) m/z 377.2 [M+H]+.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationAfter being concentrated under reduced pressure
  4. customthe residue was purified by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-70ebf947e6a44b7cb835bade7437e1ae
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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