Acetonitrile → HCID 67347093, compound

HRID 1676329Notes

Reaction equation

HRID 1676329 reaction equation
N[C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=4)[S:17][C:10]=23)=[CH:4][CH:3]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([C:38]2([C:41](F)=[O:42])[CH2:40][CH2:39]2)=[O:37])=[CH:31][CH:30]=1.CC#[N:46]>>[F:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]([C:2]2[CH:3]=[CH:4][C:5]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]4[CH:15]=[C:16]([C:18]5[CH:27]=[CH:26][C:21]([C:22](=[O:23])[NH:24][CH3:25])=[CH:20][CH:19]=5)[S:17][C:10]=34)=[CH:6][N:7]=2)[C:36]([C:38]2([C:41]([NH2:46])=[O:42])[CH2:40][CH2:39]2)=[O:37])=[CH:31][CH:30]=1

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 67347606HCID 67347606, compoundHCID 866146491-((4-Fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride

Product 1

HCID 67347093HCID 67347093, compoundYield 11%

Procedure

A stirred mixture of 4-(7-(6-aminopyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-benzamide (11 mg, 0.029 mmol) and 1-((4-fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride (9.9 mg, 0.044 mmol), in CH3CN (0.5 mL) was heated at 100° C. for 3 hours. After cooling to room temperature, the mixture was partitioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×5 mL). The combined organic phases were washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (0.5 mm thickness, Rf=0.30), eluting with 10% MeOH/CHCl3. The product was obtained as a beige solid (2 mg, 11%). HPLC: 100% purity (220 nm); LRMS (ESI+): 94% purity, 220 nm, m/z 582 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 9.59 (s, 1H), 9.01 (s, 1H), 8.53 (d, J=5 Hz, 1H), 8.29 (m, 2H), 7.85 (m, 5H), 7.55 (m, 3H), 7.04 (t, J=9 Hz, 2H), 6.56 (d, J=5 Hz, 1H), 6.19 (m, 1H), 3.06 (d, J=5 Hz, 3H), 1.82 (m, 2H), 1.68 (m, 2H).

Workup

  1. customthe mixture was partitioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL)
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc (2×5 mL)
  4. washThe combined organic phases were washed with brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by preparative TLC (0.5 mm thickness, Rf=0.30)
  9. washeluting with 10% MeOH/CHCl3

Sources & evidence

ORD record
ord-a69d7e92f28e4c4fa2e005aece517ca7
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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