Triethylamine → HCID 67980881, compound

HRID 2406977Notes

Reaction equation

HRID 2406977 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:10]1([CH:16]([NH:33][C:34]2[CH:42]=[CH:41][C:37]([C:38](O)=[O:39])=[CH:36][N:35]=2)[C:17]2[CH:18]=[N:19][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[N:21][CH:22]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.C(=O)=O.CO>ClCCl.O>[CH:10]1([CH:16]([NH:33][C:34]2[N:35]=[CH:36][C:37]([C:38]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:39])=[CH:41][CH:42]=2)[C:17]2[CH:18]=[N:19][C:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:27][CH:28]=3)=[N:21][CH:22]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21973728Carbon dioxide methanolHCID 67980893HCID 67980893, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 67980881HCID 67980881, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of ethyl 3-aminopropionate hydrochloride (487 mg, 4.15 mmol), crude (+/−)-6-[(cyclohexyl{2-[4-(trifluoromethyl)phenyl]pyrimidin-5-yl}methyl)amino]nicotinic acid (948 mg, 2.08 mmol), hydroxybenzotriazole hydrate (318 mg, 2.08 mmol), and triethylamine (1.16 ml, 8.31 mmol) in dichloromethane (21 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (442 mg, 2.28 mmol). The reaction was stirred for 12 hours at ambient temperature. The reaction was diluted with water and the organic layer was separated. The aqueous layer was extracted with dichloromethane (2×) and the combined organic layers were 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. The enantiomers were separated by chiral SFC to afford the two products (Isomer 1=50 mg, 5% and isomer 2=50 mg, 5%) as solids. Column: Chiralcel OJ-H. Dimensions: 10 mm×250 cm. Mobile Phase: 70/30 CO2/methanol. Flow Rate: 10 mL/min. Modifier: none. Isomer 1: Retention time: 2.37 minutes. Isomer 2: Retention time: 2.95 minutes. 1H NMR (400 MHz, CDCl3, δ): 8.76 (s, 2H), 8.53 (d, J=8.2 Hz, 2H), 8.43 (d, J=2.0 Hz, 1H), 7.78 (dd, J=8.7, 2.2 Hz, 1H), 7.71 (d, J=8.2 Hz, 2H), 6.71 (t, J=5.8 Hz, 1H), 6.30-6.36 (m, 1H), 5.84 (br. s., 1H), 4.68 (t, J=6.9 Hz, 1H), 4.13 (q, J=6.9 Hz, 2H), 3.65 (q, J=5.9 Hz, 2H), 2.58 (t, J=5.8 Hz, 2H), 1.95 (d, J=12.3 Hz, 1H), 1.56-1.85 (m, 6H), 1.23 (t, J=7.0 Hz, 3H), 1.04-1.20 (m, 4H). MS (M+1): 556.4.

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with dichloromethane (2×)
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified via ISCO MPLC (SiO2, 0-100% ethyl acetate in heptane)
  7. customto yield the product
  8. customThe enantiomers were separated by chiral SFC
  9. customto afford the two products (Isomer 1=50 mg, 5% and isomer 2=50 mg, 5%) as solids

Sources & evidence

ORD record
ord-69092b90176f4ae8a2a7f2f61140c638
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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