1,2-Dichloroethane → HCID 86761756, compound

HRID 1809045Notes

Reaction equation

HRID 1809045 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20](O)=[O:21])[C:15]([C:23]2[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=2)=N[CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[C:34]2[C:47](=[CH:48][CH:49]=1)[CH2:46][C:36]1([C:44]3[C:39](=[N:40][CH:41]=[CH:42][CH:43]=3)[NH:38][C:37]1=[O:45])[CH2:35]2.[CH:50]1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:30][C:25]1[CH:24]=[C:23]([C:15]2[N:16]([CH2:19][C:20](=[O:21])[NH:31][C:32]3[CH:33]=[C:34]4[C:47](=[CH:48][CH:49]=3)[CH2:46][C:36]3([C:44]5[C:39](=[N:40][CH:41]=[CH:42][CH:43]=5)[NH:38][C:37]3=[O:45])[CH2:35]4)[C:17](=[O:18])[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:13][CH:50]=2)[CH:28]=[C:27]([F:29])[CH:26]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 10001879HCID 10001879, compoundHCID 591667225-amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Product 1

HCID 86761756HCID 86761756, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [5-{[(benzyloxy)carbonyl]amino}-2-(3,5-difluorophenyl)-6-oxopyrimidin-1(6H)-yl]acetic acid (91 mg, 0.22 mmol) [Veale et al. (1995) J. Med. Chem. 38, 98], 5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (50 mg, 0.20 mmol) [Bell et al. WO 2006/031610], HOBT (34 mg, 0.22 mmol), and EDC (42 mg, 0.22 mmol) in DMF (2 mL) is stirred at ambient temperature for 18 h. The reaction mixture is purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The pure, product-containing fractions are combined and made basic with saturated aqueous NaHCO3. The resulting mixture is extracted with EtOAc (3×20 mL), and the combined organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound.

Workup

  1. customThe reaction mixture is purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionThe resulting mixture is extracted with EtOAc (3×20 mL)
  5. washthe combined organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b6ece70dbb87452ca641dcfdfa5f157a
Source dataset
uspto-grants-2013_01
Patent number
US08362005B2

Reaction notes

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