Isopropyl chloroformate → HCID 11533076, compound

HRID 1626225Notes

Reaction equation

HRID 1626225 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][C:12]=2[C:18]2[N:19]([CH3:24])[N:20]=[CH:21][C:22]=2[Br:23])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(N(C)C)=O.Cl[C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]>CS(C)=O>[CH:35]([O:34][C:32](=[O:33])[NH:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:12]([C:18]2[N:19]([CH3:24])[N:20]=[CH:21][C:22]=2[Br:23])[CH:13]=1)([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 31374DimethylacetamideHCID 58964313HCID 58964313, compound

Product 1

HCID 11533076HCID 11533076, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 4-(2-azepan-1-yl-ethoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenylamine (0.06 g, 0.1539 mmol) 2.0 mL of DMA was added isopropyl chloroformate (0.021 g, 0.1687 mmol), and the mixture was stirred at ambient temperature overnight. The reaction mixture was diluted to 5.0 mL with DMSO and purified by RP-HPLC. The proper fractions were collected and evaporated to ¼ volume and the aqueous was neutralized with 1N NaOH to a pH 9.0. Next, the product was extracted with ethyl acetate (2×, 30 mL). The pooled organic layer was dried with sodium sulfate, filtered and evaporated to dryness to afford [4-(2-Azepan-1-yl-ethoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-carbamic acid isopropyl ester as a colorless solid in 69% yield. LCMS m/z (%)=478 (M+H79Br, 100), 480 (M+H81Br, 98). 1H NMR (400 MHz, DMSO-d6) δ: 8.79 (bs, 1H), 8.69 (bs, 1H), 7.59 (s, 1H), 7.34 (d, J=2.62 Hz, 1H), 7.21-7.31 (m, 1H), 7.14 (d, J=9.04 Hz, 1H), 4.02-4.12 (m, 1H), 3.92-4.12 (m, 2H), 3.67 (s, 3H), 2.69-2.78 (m, 2H), 2.53-2.59 (m, 2H), 1.4-1.58 (bs, 8H), 1.26 (d, J=6.82 Hz, 6H).

Workup

  1. custompurified by RP-HPLC
  2. customThe proper fractions were collected
  3. customevaporated
  4. extractionNext, the product was extracted with ethyl acetate (2×, 30 mL)
  5. dry with materialThe pooled organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-669f68ad71ab4963b7c4d3f22790580b
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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