1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 69630940, compound

HRID 1408175Notes

Reaction equation

HRID 1408175 reaction equation
[C@@H:1]1([NH:11][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[CH:23]=[CH:22][C:21]=3[NH:32][C:33]([C:35]3[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=3)[C:38](O)=[O:39])=[O:34])[CH:15]=2)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:44][NH:45][CH2:46][CH2:47][CH2:48][N:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C)C1C=CN=CC=1.O>[CH3:44][N:45]([CH2:46][CH2:47][CH2:48][N:49]1[CH2:50][CH2:51][O:52][CH2:53][CH2:54]1)[C:38](=[O:39])[C:37]1[CH:41]=[CH:42][CH:43]=[C:35]([C:33]([NH:32][C:21]2[CH:22]=[CH:23][C:24]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:25][C:20]=2[C:16]2[CH:15]=[C:14]([C:12](=[O:13])[NH:11][C@@H:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH2:4][CH2:3][CH2:2]3)[CH:19]=[CH:18][N:17]=2)=[O:34])[CH:36]=1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22594078N-Methyl-3-(morpholin-4-yl)propan-1-amineHCID 66587548HCID 66587548, compound

Product 1

HCID 69630940HCID 69630940, compoundYield 52.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-((2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzoic acid (150 mg, 0.26 mmol, 1.00 equiv) in dichloromethane (3 mL), N-methyl-3-morpholinopropan-1-amine (42 mg, 0.27 mmol, 1.00 equiv), EDC.HCl (75 mg, 0.39 mmol, 1.50 equiv), 4-dimethylaminopyridine (48 mg, 0.39 mmol, 1.50 equiv). The resulting solution was stirred for 2 h at 25° C. The resulting solution was diluted with 3 mL of water. The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×5 mL of water and 2×5 mL of Brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (120 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (24% CH3CN up to 34% in 6 min); Detector, Waters2545 UvDector 254&220 nm. 97 mg product was obtained. This resulted in 97 mg (35%) of (S)—N1-methyl-N1-(3-morpholinopropyl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide. Example 126 as a yellow solid. (ES, m/z): 715 [M+H]+ (400 MHz, CD3OD, ppm): 8.91 (s, 1H), 8.73 (d, J=8.8 Hz, 1H), 8.41 (s, 1H), 8.14˜8.09 (m, 3H), 7.873˜7.857 (m, 1H), 7.753˜7.69 (m, 3H), 7.27 (d, J=7.2 Hz, 1H), 7.19˜7.13 (m, 3H), 5.40 (d, J=6.4 Hz, 1H), 4.18 (s, 2H), 3.90˜3.50 (m, 9H), 3.46˜3.17 (m, 5H), 3.07 (s, 3H), 2.89˜2.78 (s, 2H), 2.26˜2.03 (m, 8H), 1.98˜1.81 (m, 4H).

Workup

  1. extractionThe resulting solution was extracted with 2×5 mL of dichloromethane
  2. washThe resulting mixture was washed with 1×5 mL of water and 2×5 mL of Brine
  3. dry with materialThe mixture was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (120 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (24% CH3CN up to 34% in 6 min)

Sources & evidence

ORD record
ord-bea9c786e36444bf89d8e0fbdd217b18
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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