Pyridine → (1S,3S,5S)-2-((2S)-2-(3-Hydroxyadamantan-1-yl)-2-(tritylamino)acetyl)-2-azabicyclo[3.1.0]hexane-3-carbonitrile

HRID 1483178Notes

Reaction equation

HRID 1483178 reaction equation
[C:1]([NH:20][C@@H:21]([C:33]12[CH2:42][CH:37]3[CH2:38][CH:39]([CH2:41][C:35]([OH:43])([CH2:36]3)[CH2:34]1)[CH2:40]2)[C:22]([N:24]1[C@H:29]([C:30]([NH2:32])=O)[CH2:28][C@H:27]2[C@@H:25]1[CH2:26]2)=[O:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CO>[C:1]([NH:20][C@@H:21]([C:33]12[CH2:40][CH:39]3[CH2:38][CH:37]([CH2:36][C:35]([OH:43])([CH2:41]3)[CH2:34]1)[CH2:42]2)[C:22]([N:24]1[C@H:29]([C:30]#[N:32])[CH2:28][C@H:27]2[C@@H:25]1[CH2:26]2)=[O:23])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 11430Potassium CarbonateHCID 121454404(1S,3S,5S)-2-[(2S)-2-tritylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide

Product 1

HCID 121454409(1S,3S,5S)-2-((2S)-2-(3-Hydroxyadamantan-1-yl)-2-(tritylamino)acetyl)-2-azabicyclo[3.1.0]hexane-3-carbonitrileYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

A solution of (1S,3S,5S)-2-[(2S)-2-tritylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide (15.0 g) in tetrahydrofuran (150 ml) was mixed with pyridine (12.3 g) and cooled to 0-10° C. Trifluoroacetic anhydride (19.1 g) was added to the reaction mixture slowly over 30 minutes. The reaction mixture was stirred at 0-10° C. for 3 hours. Completion of the reaction was confirmed by HPLC. Aqueous potassium carbonate solution (20%, 240 ml) was added to the reaction mixture over 30 minutes to obtain pH 10-11. Methanol (50 ml) was added, and the reaction mixture was stirred at 25° C. for 3 hours. Completion of the reaction was verified using TLC. The reaction mixture was cooled to 0° C. and stirred for 30 minutes. The solid was filtered and washed with water (2×15 ml). The solid was dried under vacuum at 50-60° C. for 8 hours to give the title compound (10.0 g).

Workup

  1. customto obtain pH 10-11
  2. stirringthe reaction mixture was stirred at 25° C. for 3 hours
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. stirringstirred for 30 minutes
  5. filtrationThe solid was filtered
  6. washwashed with water (2×15 ml)
  7. customThe solid was dried under vacuum at 50-60° C. for 8 hours

Sources & evidence

ORD record
ord-8585266a749e41dd9f63f63a93d52cdf
Source dataset
uspto-grants-2016_08
Patent number
US09416105B2

Reaction notes

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