1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-4-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 919601Notes

Reaction equation

HRID 919601 reaction equation
[CH3:1][N:2]([C@H:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)[C:3]1[C:4]2[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:5]=2[N:6]=[CH:7][N:8]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:41][C:42]1[CH:43]=[C:44]([NH:49][CH2:50][C:51](O)=[O:52])[CH:45]=[C:46]([Cl:48])[CH:47]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:41][C:42]1[CH:43]=[C:44]([NH:49][CH2:50][C:51]([N:16]2[CH2:17][CH2:18][CH2:19][C@H:14]([N:2]([CH3:1])[C:3]3[C:4]4[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:5]=4[N:6]=[CH:7][N:8]=3)[CH2:15]2)=[O:52])[CH:45]=[C:46]([Cl:48])[CH:47]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 86706466(S)-4-(methyl(piperidin-3-yl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 56971630(S)-4-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneYield 9,465.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-4-(methyl(piperidin-3-yl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (150 mg, 0.6 mmol) in DMF (5 mL) was added EDCI (164 mg, 0.85 mmol), HOBt (114 mg, 0.85 mmol), 2-(3,5-dichlorophenylamino)acetic acid (126 mg, 0.57 mmol) and DIEA (147 mg, 1.14 mmol) at 0° C. The reaction mixture was stirred at rt overnight, diluted with EtOAc and washed with water. The aqueous layer was extracted with the EtOAc, the combined organic layer was dried over Na2SO4 and evaporated in vacuo to give the crude compound that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford (25 g, 9%) of the titled compound. 1H NMR (400 MHz, CD3OD): δ 8.29 (s, 1H), 6.61-6.60 (d, 1H), 6.59-6.58 (m, 2H), 4.28-4.01 (m, 1H), 3.99-3.95 (m, 2H), 3.68-3.66 (t, J=4.4 Hz, 1H), 3.57-3.54 (t, J=4.4 Hz, 1H), 3.34 (s, 3H), 3.08-2.97 (m, 3H), 2.60-2.53 (m, 2H), 2.03-2.00 (m, 2H), 1.43-1.26 (m, 3H). LC-MS: m/z [M+1]=463.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with the EtOAc
  3. dry with materialthe combined organic layer was dried over Na2SO4
  4. customevaporated in vacuo
  5. customto give the crude compound that
  6. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-ff2fd29f2d674bf09eec79c1c9865a84
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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