Methanol → 3-(2-(2-(2-(3-(3-((2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)phenyl)propoxy)ethoxy)ethoxy)ethoxy)propanoic acid

HRID 625485Notes

Reaction equation

HRID 625485 reaction equation
C([O:5][C:6](=[O:31])[CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25]([OH:27])=O)(C)(C)C.[NH2:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:35][C:34]=1[C:45]1[CH:46]=[C:47]([CH:61]=[CH:62][N:63]=1)[C:48]([NH:50][C@@H:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][CH2:53][CH2:52]1)=[O:49].CCN=C=NCCCN(C)C.Cl.CO>ClCCl.CN(C)C1C=CN=CC=1>[C@@H:51]1([NH:50][C:48]([C:47]2[CH:61]=[CH:62][N:63]=[C:45]([C:34]3[CH:35]=[C:36]([N:39]4[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]4)[CH:37]=[CH:38][C:33]=3[NH:32][C:25]([C:24]3[CH:23]=[C:22]([CH2:21][CH2:20][CH2:19][O:18][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][CH2:7][C:6]([OH:5])=[O:31])[CH:30]=[CH:29][CH:28]=3)=[O:27])[CH:46]=2)=[O:49])[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][CH2:53][CH2:52]1

Participants

7

Reactant 4

HCID 887MethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665868542-(2-amino-5-(piperidin-1-yl)phenyl)-N-((S)-1,2,3,4-tetrahydronaphthalen-1-yl)isonicotinamideHCID 665868913-(3-(2-(2-(2-(3-Tert-butoxy-3-oxopropoxy)ethoxy)ethoxy)ethoxy)propyl)benzoic acid

Product 1

HCID 867059903-(2-(2-(2-(3-(3-((2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)phenyl)propoxy)ethoxy)ethoxy)ethoxy)propanoic acid

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

This compound was prepared according to the procedure described for the synthesis of Example 251 substituting 126e in place of 25b. Into a 50-mL round-bottom flask, was placed a solution of 3-(3-(2-(2-(2-(3-tert-butoxy-3-oxopropoxy)ethoxy)ethoxy)ethoxy)propyl)benzoic acid (1.308 g, 2.97 mmol, 1.00 equiv) in dichloromethane (15 mL), 2-(2-amino-5-(piperidin-1-yl)phenyl)-N—((S)-1,2,3,4-tetrahydronaphthalen-1-yl)isonicotinamide (1.26 g, 2.96 mmol, 0.99 equiv), EDC.HCl (854.8 mg, 4.46 mmol, 1.50 equiv), 4-dimethylaminopyridine (544 mg, 4.46 mmol, 1.50 equiv). The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS/TLC (DCM:MeOH=10:1). The resulting mixture was washed with 2×20 mL of NH4Cl aq. The resulting mixture was washed with 2×20 mL of Brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10˜1:1). This resulted in 2.0 g (79%) of tert-butyl 3-(2-(2-(2-(3-(3-((2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)phenyl)propoxy)ethoxy)ethoxy)ethoxy)propanoate as yellow oil.

Workup

  1. customThis compound was prepared
  2. customInto a 50-mL round-bottom flask, was placed
  3. washThe resulting mixture was washed with 2×20 mL of NH4Cl aq. The resulting mixture
  4. washwas washed with 2×20 mL of Brine
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. customThis resulted in 2.0 g (79%) of tert-butyl 3-(2-(2-(2-(3-(3-((2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)phenyl)propoxy)ethoxy)ethoxy)ethoxy)propanoate as yellow oil

Sources & evidence

ORD record
ord-76499bb7323b430e8f51104d34e8ab81
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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