Ammonium Chloride → HCID 69809287, compound

HRID 529074Notes

Reaction equation

HRID 529074 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([C:21]3[C:16](=[CH:17][CH:18]=[C:19]([CH2:22][C:23](O)=[O:24])[CH:20]=3)[N:15]([C:26]3[C:27]4[C@H:34]([CH3:35])[CH2:33][CH2:32][C:28]=4[N:29]=[CH:30][N:31]=3)[CH2:14]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:38](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH4+].[Cl-]>C(Cl)Cl.C(Cl)Cl.CN(C=O)C>[NH2:38][C:23](=[O:24])[CH2:22][C:19]1[CH:20]=[C:21]2[C:11]3([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]3)[CH2:14][N:15]([C:26]3[C:27]4[C@H:34]([CH3:35])[CH2:33][CH2:32][C:28]=4[N:29]=[CH:30][N:31]=3)[C:16]2=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 25517Ammonium Chloride2×HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68762168HCID 68762168, compound

Product 1

HCID 69809287HCID 69809287, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of (R)-2-(1′-(tert-butoxycarbonyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)acetic acid (0.020 g, 0.042 mmol), DIEA (0.023 ml, 0.13 mmol), and HBTU (0.017 g, 0.046 mmol) in 1:1 mixture of DCM/DMF (0.2 mL) was added NH4Cl (0.0067 g, 0.13 mmol). The reaction was stirred at about room temperature overnight. An additional equivalent of DIEA and NH4Cl were added and the reaction stirred at about room temperature overnight. The reaction was diluted with DCM, washed with saturated NaHCO3 and brine, dried over MgSO4, filtered, and concentrated. The crude residue was purified by column chromatography (3-5% MeOH/DCM) to yield (R)-tert-butyl 5-(2-amino-2-oxoethyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.012 g, 60%). LCMS (APCI+) m/z 478.3 [M+H]+; Rt=3.05 min.

Workup

  1. stirringthe reaction stirred at about room temperature overnight
  2. washwashed with saturated NaHCO3 and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by column chromatography (3-5% MeOH/DCM)

Sources & evidence

ORD record
ord-b477bc7ee3364eedb4366fdf1443c0ad
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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