1,2-Dichloroethane → HCID 71522976, compound

HRID 1473814Notes

Reaction equation

HRID 1473814 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([O:11][CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH2:19][CH2:18]2)[CH:8]=[C:7]([F:28])[C:3]=1[C:4]([OH:6])=O.C(Cl)CCl.C1C=C[C:36]2N(O)N=[N:39][C:37]=2[CH:38]=1.CCN(C(C)C)C(C)C.C1(N)CC1>C(Cl)Cl>[CH:37]1([NH:39][C:4](=[O:6])[C:3]2[C:2]([F:1])=[CH:10][C:9]([O:11][CH2:12][CH2:13][C@@H:14]3[CH2:16][C@@H:15]3[CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH2:19][CH2:18]3)=[CH:8][C:7]=2[F:28])[CH2:38][CH2:36]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71522974HCID 71522974, compound

Product 1

HCID 71522976HCID 71522976, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,6-Difluoro-4-(2-{(1S,2R)-2-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]cyclopropyl}ethoxy)benzoic acid (40 mg, 0.098 mmol) in 0.5 mL of DCM was stirred with EDC (37.6 mg, 0.196 mmol), HOBt (30 mg, 0.196 mmol) and DIPEA (64 mg, 0.49 mmol) at RT for 15 min. Cyclopropylamine (11.2 mg, 0.196 mmol) was added. The reaction mixture was stirred overnight. Solvent was removed under vacuum. The residue was purified by mass directed RPHPLC. The product fraction was basified with 2 M sodium bicarbonate aq. solution. The product was extracted with EtOAc. The organic layer was dried with sodium sulfate and concentrated to yield Example 3. LCMS calc: 446.45; obs: 447.01 (M+1); Human GPR119 EC50: 5.28 nM.

Workup

  1. customSolvent was removed under vacuum
  2. customThe residue was purified by mass
  3. extractionThe product was extracted with EtOAc
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. concentrationconcentrated
  6. customto yield Example 3

Sources & evidence

ORD record
ord-76136e55c64543f1a4cb18f4f69c8401
Source dataset
uspto-grants-2015_04
Patent number
US09018200B2

Reaction notes

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