1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86706440, compound

HRID 919560Notes

Reaction equation

HRID 919560 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[C:6]([F:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH:35]1[CH2:40][CH2:39][CH2:38][C@@H:37]([NH:41][C:42]2[N:47]=[CH:46][N:45]=[C:44]3[NH:48][N:49]=[CH:50][C:43]=23)[CH2:36]1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[NH:48]1[C:44]2=[N:45][CH:46]=[N:47][C:42]([NH:41][C@@H:37]3[CH2:38][CH2:39][CH2:40][N:35]([C:11](=[O:13])[CH2:10][NH:9][C:4]4[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([Cl:1])[CH:3]=4)[CH2:36]3)=[C:43]2[CH:50]=[N:49]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67515603HCID 67515603, compoundHCID 68070433HCID 68070433, compound

Product 1

HCID 86706440HCID 86706440, compoundYield 10.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled solution of 2-(3-chloro-5-fluorophenylamino)acetic acid (70 mg, 0.34 mmol) at 0° C. in DMF (5 mL), HOBt (69 mg, 0.51 mmol) was added and the reaction mixture was stirred for 10 min. before EDCI (101 mg 0.51 mmol), (R)—N-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (75 mg, 0.34 mmol) and DIEA (104 mg, 0.80 mmol) were added in succession. The reaction mixture was allowed to warm to rt and was stirred overnight. After completion of the reaction as indicated by TLC the reaction mixture was diluted with EtOAc (50 mL) and was washed with water (3×20 mL). The EtOAc layer was then dried over Na2SO4 and evaporated in vacuo to give a residue that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford the titled compound (14 mg, 10%). 1H NMR (400 MHz, CD3OD): δ 8.52-8.43 (m, 1H), 6.45-6.08 (m, 4H), 4.49-3.82 (m, 5H), 3.31-2.95 (m, 2H), 1.96-1.63 (m, 4H). LC-MS: m/z [M+1]=404.

Workup

  1. additionwere added in succession
  2. customAfter completion of the reaction
  3. washwas washed with water (3×20 mL)
  4. dry with materialThe EtOAc layer was then dried over Na2SO4
  5. customevaporated in vacuo
  6. customto give a residue that
  7. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-250cf2208e134448a80cc133bef01401
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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