1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44512059, compound

HRID 1782589Notes

Reaction equation

HRID 1782589 reaction equation
C(O[C:6](=[O:36])[NH:7][CH2:8][CH2:9][C@H:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]#[N:35])[N:29]=2)[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[CH2:14][CH2:13]1)[CH3:11])(C)(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:58][C:59]1[N:67]=[CH:66][CH:65]=[C:64]([CH3:68])[C:60]=1C(O)=O.CCN(C(C)C)C(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O.CN(C=O)C>[Cl:58][C:59]1[N:67]=[CH:66][CH:65]=[C:64]([CH3:68])[C:60]=1[C:6]([NH:7][CH2:8][CH2:9][C@H:10]([N:12]1[CH2:13][CH2:14][CH:15]([N:18]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]#[N:35])[N:29]=2)[C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH2:16][CH2:17]1)[CH3:11])=[O:36]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 154837662-Chloro-4-methylpyridine-3-carboxylic acidHCID 68973519HCID 68973519, compound

Product 1

HCID 44512059HCID 44512059, compoundYield 35.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-(3-{4-[(6-Cyano-pyridin-2-ylmethyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester (0.070 g, 0.14 mmol) was dissolved in a 3:1 mixture of CH2Cl2 and TFA and the mixture was stirred at room temperature for 1 h. The solvent was removed in vacuo and the resulting brown oil dried in vacuo (high vacuum system) for 2 h. The resulting amine, EDCI (0.030 g, 0.0.16 mmol) and HOBT (0.021 g, 0.16 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added 2-chloro-4-methyl-nicotinic acid (0.027 g, 0.16 mmol) followed by DIPEA (163 μL, 0.94 mmol) and the resulting mixture was stirred at 25° C. for 16 h. Standard workup according to General Procedure C gave the crude product as a tan oil. Purification by column chromatography on silica gel (Et2O:MeOH:NH4OH, 90:8:2, v/v/v) afforded 2-chloro-N-((R)-3-{4-[(6-cyano-pyridin-2-ylmethyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-4-methyl-nicotinamide (0.027 g, 35%) as a white foam. 1H NMR (CDCl3) δ 0.94 (m, 1H), 1.00 (d, 3H, J=6.0 Hz), 1.20 (m, 1H), 1.53 (m, 1H), 1.77 (m, 3H), 2.14 (br t, 1H), 2.41 (s, 3H), 2.54 (br t, 1H), 2.80-2.96 (m, 3H), 3.33-3.47 (m, 2H), 3.71 (s, 3H), 3.88 (s+m, 3H), 6.61 (d, 2H, J=9.0 Hz), 6.72 (d, 2H, J=9.0 Hz), 7.16 (d, 1H, J=4.5 Hz), 7.43 (d, 1H, J=9.0 Hz), 7.54 (d, 1H, J=9.0 Hz), 7.67 (t, 1H, J=9.0 Hz), 8.14 (d, 1H, J=4.5 Hz), 8.77 (br s, 1H). ES-MS m/z 547 (M+H), 569 (M+Na). Anal. Calcd. for C30H35N6O2Cl.0.2 CH2Cl2: C, 64.30; H, 6.33; N, 14.90. Found: C, 64.10; H, 6.39; N, 14.74.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe resulting brown oil dried in vacuo (high vacuum system) for 2 h
  3. customto give a pale yellow solution
  4. stirringthe resulting mixture was stirred at 25° C. for 16 h
  5. customgave the crude product as a tan oil
  6. customPurification by column chromatography on silica gel (Et2O:MeOH:NH4OH, 90:8:2, v/v/v)

Sources & evidence

ORD record
ord-e725ff071635471b80f28a376be5b3e6
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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