Dichloromethane → tert-butyl 2-(4-chloro-3-fluorobenzyl)-3-((S)-3-methyl-4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamate

HRID 82362Notes

Reaction equation

HRID 82362 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][C@@H:14]3[CH3:19])=[N:10][CH:9]=[N:8][C:7]=2[CH2:6][CH2:5]1.C(N([CH2:25][CH3:26])CC)C.[C:27]([O:31][C:32]([NH:34][C:35]([CH2:40][C:41]1[CH:46]=[CH:45][C:44](Cl)=C(F)C=1)(C)C(O)=O)=[O:33])([CH3:30])([CH3:29])[CH3:28].CN([C:52]([O:56]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[F:66][P-](F)(F)(F)(F)F.[CH2:73]([Cl:75])Cl>>[Cl:75][C:73]1[CH:44]=[CH:45][C:46]([CH2:41][CH:40]([C:52]([N:16]2[CH2:17][CH2:18][N:13]([C:11]3[C:12]4[C@H:4]([CH3:3])[CH2:5][CH2:6][C:7]=4[N:8]=[CH:9][N:10]=3)[C@@H:14]([CH3:19])[CH2:15]2)=[O:56])[CH2:35][NH:34][C:32](=[O:33])[O:31][C:27]([CH3:28])([CH3:29])[CH3:30])=[CH:26][C:25]=1[F:66]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67339039HCID 67339039, compoundHCID 86618947(Tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoic acid

Product 1

HCID 67338680tert-butyl 2-(4-chloro-3-fluorobenzyl)-3-((S)-3-methyl-4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamateYield 72%

Procedure

To a solution of (R)-5-methyl-4-((S)-2-methylpiperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (prepared according to Example 3, Steps 1 and 2; 32 mg, 0.14 mmol) in DCM (5 mL) were added triethylamine (1 mL), 3-((tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoic acid (46 mg, 0.14 mmol) and HBTU (52 mg, 0.14 mmol). The mixture was stirred at room temperature for 1 hour. The solvent was removed and the residue was purified by silica gel chromatography, eluting with ethyl acetate to afford tert-butyl 2-(4-chloro-3-fluorobenzyl)-3-((S)-3-methyl-4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamate (50 mg, 72%). 1H NMR (CDCl3, 400 MHz) δ 8.44 (m, 1H), 7.28 (m, 1H), 7.05-6.80 (m, 2H), 5.10-4.90 (m, 1H), 4.70-4.30 (m, 1H), 4.10-3.70 (m, 1H), 3.40-3.20 (m, 2H), 3.00-2.80 (m, 2H), 2.20 (m, 1H), 1.70 (m, 1H), 1.43 (s, 9H), 1.25-0.70 (m, 6H). MS (APCI+) [M+H]+546.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-49ca27d754ea4326bfae3906ac8f8c53
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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