Diisopropylethylamine → HCID 71467508, compound

HRID 336990Notes

Reaction equation

HRID 336990 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([C:19](O)=[O:20])=[C:16]4[CH2:22][CH2:23][CH2:24][CH2:25][C:15]=34)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:64][C@@H:65]1[CH2:69][CH2:68][NH:67][C:66]1=[O:70]>C(Cl)Cl.O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:26]([F:28])([F:29])[F:27])[O:13][N:12]=[C:11]([C:14]3[S:18][C:17]([C:19]([NH:64][C@@H:65]4[CH2:69][CH2:68][NH:67][C:66]4=[O:70])=[O:20])=[C:16]4[CH2:22][CH2:23][CH2:24][CH2:25][C:15]=34)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67280940(3R)-3-Aminopyrrolidin-2-one--hydrogen chloride (1/1)HCID 71471630HCID 71471630, compound

Product 1

HCID 71467508HCID 71467508, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Stir a mixture of 3-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (850 mg, 1.84 mmol), HATU (837 mg, 2.20 mmol) and DIEA (539 mg, 0.8 mL, 4.6 mmol) in DCM (8 mL) at room temperature for 15 min, followed by addition of (R)-3-aminopyrrolidin-2-one hydrochloride (315 mg, 2.76 mmol). Stir the reaction mixture at room temperature for additional 1.5 hour. Dilute the reaction mixture with water (20 mL) and extract with DCM (20 mL×3). The combined organic layers are washed brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by preparative HPLC to afford 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((R)-2-oxopyrrolidin-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxamide as a white solid (730 mg, 73.0%). MS (m/z): 546 (M+1); 1H NMR (400 MHz, CDCl3) δ 7.52-7.46 (m, 3H), 6.49 (s, 1H), 5.83 (s, 1H), 4.51-4.48 (m, 1H), 4.22 (d, J=17.2, 1H), 3.85 (d, J=17.2, 1H), 3.52-3.47 (m, 2H), 3.09-2.87 (m, 5H), 2.12-2.03 (m, 1H), 1.89-1.73 (m, 4H).

Workup

  1. stirringStir the reaction mixture at room temperature for additional 1.5 hour
  2. extractionextract with DCM (20 mL×3)
  3. washThe combined organic layers are washed brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under vacuum
  6. customPurify the residue by preparative HPLC

Sources & evidence

ORD record
ord-0d16ec76e49040c9b047829707cecc38
Source dataset
uspto-grants-2014_11
Patent number
US08889710B2

Reaction notes

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