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Acetyl chloride → (5R,7R)-4-(4-(acetamidomethyl)-1'-benzylspiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 529107
Notes
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Reaction equation

HRID 529107 reaction equation
Cl.Cl.Cl.[N+:4]([C:7]1[CH:48]=[CH:47][C:10]([C:11]([O:13][C@H:14]2[C:18]3[N:19]=[CH:20][N:21]=[C:22]([N:23]4[C:43]5[C:38](=[C:39]([CH2:44][NH2:45])[CH:40]=[CH:41][CH:42]=5)[C:25]5([CH2:30][CH2:29][N:28]([CH2:31][C:32]6[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=6)[CH2:27][CH2:26]5)[CH2:24]4)[C:17]=3[C@H:16]([CH3:46])[CH2:15]2)=[O:12])=[CH:9][CH:8]=1)([O-:6])=[O:5].CCN(CC)CC.[C:56](Cl)(=[O:58])[CH3:57]>C(Cl)Cl>[N+:4]([C:7]1[CH:8]=[CH:9][C:10]([C:11]([O:13][C@H:14]2[C:18]3[N:19]=[CH:20][N:21]=[C:22]([N:23]4[C:43]5[C:38](=[C:39]([CH2:44][NH:45][C:56](=[O:58])[CH3:57])[CH:40]=[CH:41][CH:42]=5)[C:25]5([CH2:30][CH2:29][N:28]([CH2:31][C:32]6[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=6)[CH2:27][CH2:26]5)[CH2:24]4)[C:17]=3[C@H:16]([CH3:46])[CH2:15]2)=[O:12])=[CH:47][CH:48]=1)([O-:6])=[O:5]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 69812752(5R,7R)-4-(4-(aminomethyl)-1'-benzylspiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate trihydrochloride

Product 1

HCID 69811912(5R,7R)-4-(4-(acetamidomethyl)-1'-benzylspiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateYield 103.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (5R,7R)-4-(4-(aminomethyl)-1′-benzylspiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate trihydrochloride (30 mg, 0.042 mmol) and Et3N (0.034 mL, 0.19 mmol) in DCM (1 mL) was added acetyl chloride (0.0033 mL, 0.046 mmol) at about 0° C. under N2. The reaction was stirred at about 0° C. for about 30 minutes and diluted with DCM. The reaction mixture was washed with saturate aqueous NaHCO3 solution and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (2% MeOH/DCM) to give (5R,7R)-4-(4-(acetamidomethyl)-1′-benzylspiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (28 mg, 68%) as an oil. LCMS (APCI+) m/z 647 [M+H]+; Rt=3.21 min.

Workup

  1. washThe reaction mixture was washed with saturate aqueous NaHCO3 solution and brine
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography on silica gel (2% MeOH/DCM)

Sources & evidence

ORD record
ord-58079ce0cc254836bb9769ac7ecc6972
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09346805B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes