1,1'-Carbonyldiimidazole → HCID 60198467, compound

HRID 2279488Notes

Reaction equation

HRID 2279488 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]([NH2:27])[CH2:22][C:23]([F:26])([F:25])[F:24])[CH:17]=[CH:18][C:19]=1[Cl:20].CCN(C(C)C)C(C)C.[N:37]1[C:42]2[CH2:43][NH:44][CH2:45][CH2:46][C:41]=2[CH:40]=[N:39][C:38]=1[NH:47][C@@H:48]([CH3:51])[CH2:49][OH:50]>C(Cl)Cl.CN(C=O)C>[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]([NH:27][C:6]([N:44]2[CH2:45][CH2:46][C:41]3[CH:40]=[N:39][C:38]([NH:47][C@@H:48]([CH3:51])[CH2:49][OH:50])=[N:37][C:42]=3[CH2:43]2)=[O:7])[CH2:22][C:23]([F:24])([F:25])[F:26])[CH:17]=[CH:18][C:19]=1[Cl:20]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2×HCID 43167237HCID 43167237, compoundHCID 68295199HCID 68295199, compound

Product 1

HCID 60198467HCID 60198467, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A 40 mL vial was charged with CDI (0.584 g, 3.60 mmol), 1-(3,4-dichlorophenyl)-3,3,3-trifluoropropan-1-amine (0.929 g, 3.60 mmol), DIPEA (1.88 mL, 10.8 mmol), DCM (7 mL) and DMF (2 mL). The mixture was stirred for 30 min then a solution of 138 (0.750 g, 3.60 mmol) and DIPEA (1.88 mL, 10.8 mmol) in DCM (3 mL) was added and the mixture stirred for 18 h. The reaction mixture was washed with brine (4 mL) and the organic phase isolated and concentrated. The residue was resuspended in EtOAc and washed with brine (2×50 mL) and concentrated in vacuo. The crude product was purified by reverse phase chromatography (Horizen C18 Biotage 40M) eluting with a MeCN/H2O gradient (eluted at ca. 50% MeCN) to afford 925 mg which was separated by chiral HPLC chromatography and repurified as described in example 19 to afford 0.212 g (23%) of I-34 as a white solid: 1H NMR (400 MHz, CD3OD) δ 8.06 (s, 1H), 7.55 (m, 1H), 7.49 (d, 1H), 7.31 (m, 1H), 5.20 (m, 1H), 4.41 (q, 2H), 4.06 (m, 1H), 3.65 (t, 2H), 3.56 (m, 2H), 2.79 (m, 4H), 1.20 (d, 3H); m/z (APCI-pos) M+1=492.0.

Workup

  1. stirringthe mixture stirred for 18 h
  2. washThe reaction mixture was washed with brine (4 mL)
  3. customthe organic phase isolated
  4. concentrationconcentrated
  5. washwashed with brine (2×50 mL)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by reverse phase chromatography (Horizen C18 Biotage 40M)
  8. washeluting with a MeCN/H2O gradient (eluted at ca. 50% MeCN)
  9. customto afford 925 mg which
  10. customwas separated by chiral HPLC chromatography
  11. customrepurified
  12. customto afford 0.212 g (23%) of I-34 as a white solid

Sources & evidence

ORD record
ord-e7d72f2d34ad48f5acbba42ab5d45778
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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