Triethylamine → HCID 24950096, compound

HRID 625035Notes

Reaction equation

HRID 625035 reaction equation
Cl.Cl.[CH3:3][C@H:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[CH2:6][S:5]1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH2:30][N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:27](O)=[O:28])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH2:30][N:31]2[CH2:32][CH2:33][CH2:34][CH2:35]2)[C:27]([N:16]2[CH2:17][CH2:18][N:13]([C:11]3[C:12]4[C@H:4]([CH3:3])[S:5][CH2:6][C:7]=4[N:8]=[CH:9][N:10]=3)[CH2:14][CH2:15]2)=[O:28])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673399992-(4-Chlorophenyl)-3-(pyrrolidin-1-yl)propanoic acidHCID 67459940HCID 67459940, compound

Product 1

HCID 24950096HCID 24950096, compoundYield 46.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (1 g, 3.23 mmol) and 2-(4-chlorophenyl)-3-(pyrrolidin-1-yl)propanoic acid (2 g, 7.88 mmol) in DCM (40 mL) were added HBTU (1.5 g, 3.96 mmol) and triethylamine (2.75 mL, 19.8 mmol). The mixture was stirred at room temperature for 1 hour. The solvent was removed, and the residue was dissolved in ethyl acetate (200 mL) and washed with brine (5×100 mL) and water (3×100 mL). The organic phase was dried and concentrated. The residue was purified by silica gel chromatography, eluting with ethyl acetate-DCM/MeOH (20:1) to give 2-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one (0.713 g, 46.7%). 1H NMR (CDCl3, 400 MHz) δ 8.47 (s, 1H), 7.38-7.28 (m, 4H), 4.75 (m, 1H), 4.54 (m, 1H), 4.17 (m, 2H), 3.88-3.25 (m, 14H), 2.12 (m, 4H), 1.43 (m, 3H). MS (APCI+) [M+H]+ 473.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  3. washwashed with brine (5×100 mL) and water (3×100 mL)
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with ethyl acetate-DCM/MeOH (20:1)

Sources & evidence

ORD record
ord-e1002aaea4754928a5e113cd324cbf35
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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