Diisopropylethylamine → HCID 89404252, compound

HRID 1487003Notes

Reaction equation

HRID 1487003 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:25]12[CH:30]([NH:31][C:32](=[O:48])[O:33][CH2:34][CH:35]3[C:47]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:41]4[C:36]3=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH:29]1[CH2:28][NH:27][CH2:26]2.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:24][C:2]([F:1])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([N:27]3[CH2:26][CH:25]4[CH:29]([CH:30]4[NH:31][C:32](=[O:48])[O:33][CH2:34][CH:35]4[C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][C:41]=5[C:42]5[C:47]4=[CH:46][CH:45]=[CH:44][CH:43]=5)[CH2:28]3)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 71247447HCID 71247447, compoundHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 89404252HCID 89404252, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

(Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (1.0 g, 1.0 eq.) was dissolved in DCM (50 mL) and cooled to −60° C. where (9H-fluoren-9-yl)methyl 3-azabicyclo[3.1.0]hexan-6-ylcarbamate (1.09 g, 1.2 eq.), T3P (50% in EtOAc) (2.02 mL, 1.2 eq.) and DIPEA (0.95 mL, 2 eq.) was added. The clear reaction mixture was stirred at −60° C. for 1 h, quenched with water, and extracted with DCM. The organic layer was dried over sodium sulphate, concentrated under reduced pressure (25° C., 20 mm Hg) to afford the crude product, which was purified by chromatography (2% Methanol in DCM) to yield (Z)-(9H-fluoren-9-yl)methyl (3-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acryloyl)-3-azabicyclo[3.1.0]hexan-6-yl)carbamate (1.26 g, 69% yield).

Workup

  1. additionwas added
  2. customquenched with water
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure (25° C., 20 mm Hg)
  6. customto afford the crude product, which
  7. customwas purified by chromatography (2% Methanol in DCM)

Sources & evidence

ORD record
ord-2fc9a1e78db94917a72b39e15b7455da
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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