Tetrafluoro-m-phenylenediamine dihydrochloride → Ammonium Hydroxide

HRID 1064201Notes

Reaction equation

HRID 1064201 reaction equation
[C:1]([O:5][C:6](=[O:40])[NH:7][C@H:8]([CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)[C:9](=[O:33])[NH:10][N:11]1[C:19]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:20](=[O:24])[NH:21][N:22]=[CH:23][C:13]([C:14]=23)=[C:12]1[C:25](=[O:32])[NH:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])([CH3:4])([CH3:3])[CH3:2].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.C(OC(N[C@H](C1CCCCC1)C(O)=O)=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.CN(C)C=O.CO>[OH-:5].[NH4+:7].[C:1]([O:5][C:6](=[O:40])[NH:7][C@H:8]([CH:34]1[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]1)[C:9](=[O:33])[NH:10][N:11]1[C:19]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:20](=[O:24])[NH:21][N:22]=[CH:23][C:13]([C:14]=23)=[C:12]1[C:25](=[O:32])[NH:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7014890(2R)-[(tert-Butoxycarbonyl)amino](cyclohexyl)acetic acidHCID 69746610(R)-(Cyclohexyl-[2-(2-dimethylamino-ethylcarbamoyl)-6-oxo-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-ylcarbamoyl]-methyl)-carbamic Acid tert-butyl Ester

Product 2

HCID 14923Ammonium HydroxideHCID 69746610(R)-(Cyclohexyl-[2-(2-dimethylamino-ethylcarbamoyl)-6-oxo-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-ylcarbamoyl]-methyl)-carbamic Acid tert-butyl Ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Preparation of intermediate 228(a) from Intermediate 171(a) of Example 171 (200 mg, 0.571 mmol), (R)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (147 mg, 0.571 mmol), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (131 mg, 0.686 mmol), and 4-dimethylaminopyridine (84 mg, 0.688 mmol) in N,N-dimethylformamide (8.0 mL) was carried out analogously to Example 190, step 2. When the reaction was judged complete, the volatile components were removed in vacuo, and the resulting residue was dissolved in methanol and loaded onto a silica gel plug. The plug was then loaded onto a silica gel column and eluted with 40:3:0.3 dichloromethane: methanol: ammonium hydroxide to afford Intermediate 228(a) (77 mg, 0.139 mmol) as a yellow solid in 24% yield.

Workup

  1. customthe volatile components were removed in vacuo
  2. dissolutionthe resulting residue was dissolved in methanol
  3. washeluted with 40:3:0.3 dichloromethane

Sources & evidence

ORD record
ord-66b3ae33364b44f496e82ede2e5bcc5d
Source dataset
uspto-grants-2005_11
Patent number
US06967198B2

Reaction notes

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