Diisopropylethylamine → (S)-tert-Butyl 4-(1-cyano-2-(4'-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216990Notes

Reaction equation

HRID 216990 reaction equation
[NH2:1][C:2](=O)[C@@H:3]([NH:19][C:20]([C:22]1([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C>[C:2]([C@@H:3]([NH:19][C:20]([C:22]1([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C:17]#[N:18])=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)#[N:1]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 59568597(S)-tert-Butyl 4-(1-amino-3-(4'-cyanobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568556(S)-tert-Butyl 4-(1-cyano-2-(4'-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 77.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
68 °C

Procedure

To a solution of (S)-tert-butyl 4-(1-amino-3-(4′-cyanobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (produced in step (ii), 35 g) in DMF (2.5 rel. vol.) at room temperature was added diisopropylethylamine (4 mol. eq.) and T3P in DMF (50% wt/wt in DMF, 3 mol. eq.) under nitrogen. The resulting mixture was heated to 68° C. for 2 h. The reaction mixture was cooled to room temperature and quenched by dropwise addition of water (3 rel. vol.). The reaction mixture was stirred for 30 min and 2-methyltetrahydrofuran (15 rel. vol.) was added. The organic layer was washed with water (2×5 rel. vol.) followed is by saturated aqueous sodium hydrogen carbonate solution. The separated organic layer was concentrated to 10 rel. vol. under reduced pressure and then heated to 55° C. after which n-heptane (5 rel. vol.) was slowly added over a period of 15 min. The mixture was stirred for 30 min at 55° C. and then filtered, washed with n-heptane (2 rel. vol.) and dried at 50° C. to afford the sub-titled compound (26.2 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched by dropwise addition of water (3 rel. vol.)
  3. addition2-methyltetrahydrofuran (15 rel. vol.) was added
  4. washThe organic layer was washed with water (2×5 rel. vol.)
  5. concentrationThe separated organic layer was concentrated to 10 rel
  6. temperaturevol. under reduced pressure and then heated to 55° C. after which n-heptane (5 rel. vol.)
  7. additionwas slowly added over a period of 15 min
  8. stirringThe mixture was stirred for 30 min at 55° C.
  9. filtrationfiltered
  10. washwashed with n-heptane (2 rel. vol.)
  11. customdried at 50° C.

Sources & evidence

ORD record
ord-89ba2b3bf84b4a76b77b6930e2b51c3c
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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