Hydrochloric Acid → Ammonium Hydroxide

HRID 1615854Notes

Reaction equation

HRID 1615854 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:49])[N:18]([CH2:19][CH2:20][S:21][C:22]3[CH:23]=[C:24]4[C:45](=[CH:46][CH:47]=3)[CH2:44][C@:26]3([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[N:28](C[O:36]CC[Si](C)(C)C)[C:27]3=[O:43])[CH2:25]4)[C:17](=[O:48])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.Cl.C(N)CN>CO>[NH4+:11].[OH-:36].[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:49])[N:18]([CH2:19][CH2:20][S:21][C:22]3[CH:23]=[C:24]4[C:45](=[CH:46][CH:47]=3)[CH2:44][C@:26]3([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[NH:28][C:27]3=[O:43])[CH2:25]4)[C:17](=[O:48])[C:12]3([CH2:13][CH2:14][CH2:15][CH2:16]3)[NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3301EthylenediamineHCID 66864406HCID 66864406, compound

Product 2

HCID 14923Ammonium HydroxideHCID 44468990HCID 44468990, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (2R)-5-({2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]ethyl}sulfanyl)-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one from Step A (69 mg, 0.098 mmol) in MeOH (10 mL) was saturated with HCl (g). After 1 h the mixture was resaturated with HCl (g), aged for 2 h, and then concentrated in vacuo. The residue was dissolved in MeOH (5 mL) and treated with ethylenediamine (0.033 mL, 0.489 mmol) to adjust the mixture to pH 10. After 2 h, the reaction mixture was concentrated in vacuo, and the crude product was purified on silica gel, eluting with a gradient of CH2Cl2:CH3OH:NH4OH—100:0:0 to 90:10:0.1, to yield the title compound. MS: m/z=575 (M+1). HRMS: m/z=575.2281; calculated m/z=575.2287 for C32H33F2N4O2S.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in MeOH (5 mL)
  3. waitAfter 2 h
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customthe crude product was purified on silica gel
  6. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-d3839a0b1df74a8c9dfdb05532e694c9
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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