Cesium carbonate → tert-Butyl 3-(3-(aminocarbonyl)-5-ethyl-4-{[(5-iodo-2-propoxy-3-Pyridinyl)carbonyl]amino}-1H-pyrazol-1-yl)-1-azetidinecarboxylate

HRID 1636007Notes

Reaction equation

HRID 1636007 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]([C:10]1[C:14]([NH:15][C:16](=[O:28])[C:17]2[CH:22]=[C:21]([I:23])[CH:20]=[N:19][C:18]=2[O:24][CH2:25][CH2:26][CH3:27])=[C:13]([CH2:29][CH3:30])[NH:12][N:11]=1)=[O:9].I[CH:32]1[CH2:35][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]1>CN(C)C=O>[NH2:7][C:8]([C:10]1[C:14]([NH:15][C:16]([C:17]2[C:18]([O:24][CH2:25][CH2:26][CH3:27])=[N:19][CH:20]=[C:21]([I:23])[CH:22]=2)=[O:28])=[C:13]([CH2:29][CH3:30])[N:12]([CH:32]2[CH2:33][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35]2)[N:11]=1)=[O:9]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 11532334HCID 11532334, compound

Product 1

HCID 11585196tert-Butyl 3-(3-(aminocarbonyl)-5-ethyl-4-{[(5-iodo-2-propoxy-3-Pyridinyl)carbonyl]amino}-1H-pyrazol-1-yl)-1-azetidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (3.59 mmol) was added to a stirred solution of the product from stage b) (1.79 mmol) and the product from stage c) (2.15 mmol) in N,N-dimethylformamide (10 ml) under a nitrogen atmosphere. The mixture was heated at 80° C. for 24 h. The mixture was cooled and extracted from water with ethyl acetate. The organics were dried (MgSO4) and concentrated to give a brown oil. Purification by flash column chromatography (gradient elution from 100% dichloromethane to 90% dichloromethane/MeOH) gave the title product; 1H NMR (400 MHz, DMSO): δ=0.95 (t, 3H), 1.05 (t, 3H), 1.40 (s, 9H), 1.78-1.88 (m, 2H), 2.68 (q, 2H), 4.22-4.35 (m, 4H), 4.40 (t, 2H), 5.3 1H), 7.35 (bs, 1H), 7.52 (bs, 1H), 8.40 (s, 1H), 8.55 (s, 1H), 10.10 (s, 1H); LRMS (TSP—positive ion) 373.2 (MH+—BOC and I); Anal. Found C, 45.11; H, 5.07; N, 13.56 Calcd for C23H31O5N6I. 0.2 DCM: C, 45.28;H, 5.14; N, 13.66.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted from water with ethyl acetate
  3. dry with materialThe organics were dried (MgSO4)
  4. concentrationconcentrated
  5. customto give a brown oil
  6. customPurification
  7. washby flash column chromatography (gradient elution from 100% dichloromethane to 90% dichloromethane/MeOH)

Sources & evidence

ORD record
ord-76150beb30694eefac8ddf662ae5c884
Source dataset
uspto-grants-2003_01
Patent number
US06512002B2

Reaction notes

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