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Triethylamine → (S)-ethyl N-({6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]pyridin-3-yl}carbonyl)-beta-alaninate

HRID 2173832
Notes
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Reaction equation

HRID 2173832 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:10][CH:11]([CH3:40])[CH2:12][C@H:13]([NH:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][N:32]=1)[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=2)=[CH:16][CH:15]=1.O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:10][CH:11]([CH3:40])[CH2:12][C@H:13]([NH:30][C:31]1[N:32]=[CH:33][C:34]([C:35]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:36])=[CH:38][CH:39]=1)[C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][N:21]=2)=[CH:18][CH:19]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67980958(S)-6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinic acidHCID 178526939HCID 178526939, compound

Product 1

HCID 68061979
(S)-ethyl N-({6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]pyridin-3-yl}carbonyl)-beta-alaninate
Yield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of ethyl 3-aminopropionate hydrochloride (41.1 g, 268 mmol), (S)-6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinic acid (57.51 g, 133.9 mmol), hydroxybenzotriazole hydrate (20.5 g, 134 mmol), and triethylamine (103 ml, 737 mmol) in dichloromethane (1.34 L) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (38.9 g, 201 mmol) at ambient temperature. The reaction was heated to 40° C. for 12 hours. The reaction was diluted with saturated aqueous sodium bicarbonate (1.5 L) and the organic layer was separated. The aqueous layer was extracted with dichloromethane (2×500 ml) and the combined organic layers were washed with brine (1 L), then dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via ISCO MPLC (SiO2, 0-100% ethyl acetate in heptane) to yield the product (60.9 g, 86%) as a white foam. 1H NMR (400 MHz, CDCl3, δ): 8.93 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 7.95-8.02 (m, 3H), 7.81 (d, J=8.6 Hz, 1H), 7.78 (dd, J=9.1, 2.4 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 6.73 (t, J=5.7 Hz, 1H), 6.29 (d, J=8.8 Hz, 1H), 5.81-5.91 (m, 1H), 4.76 (q, J=6.8 Hz, 1H), 4.10-4.16 (m, 2H), 3.67 (q, J=6.1 Hz, 2H), 2.60 (t, J=5.9 Hz, 2H), 1.77-1.87 (m, 1H), 1.65-1.77 (m, 2H), 1.23-1.28 (m, 3H), 1.01 (d, J=6.1 Hz, 3H), 0.97 (d, J=6.1 Hz, 3H). MS (M+1): 529.3.

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with dichloromethane (2×500 ml)
  3. washthe combined organic layers were washed with brine (1 L)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified via ISCO MPLC (SiO2, 0-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ba585a8da174488a96e657ed44b1d039
Source dataset
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09056834B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes