Diisopropylethylamine → HCID 11671294, compound

HRID 1626191Notes

Reaction equation

HRID 1626191 reaction equation
[CH:1]12[N:7]([CH2:8][CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][C:12]=3[C:18]3[N:19]([CH3:24])[N:20]=[CH:21][C:22]=3[Br:23])[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.C1C([N+]([O-])=O)=CC=C([Cl-][C:35]([O-])=[O:36])C=1.[F:38][C:39]1[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:40]=1[CH2:41][NH2:42].C(N(CC)C(C)C)(C)C>ClCCCl>[CH:4]12[N:7]([CH2:8][CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:35]([NH:42][CH2:41][C:40]4[CH:43]=[CH:44][C:45]([F:47])=[CH:46][C:39]=4[F:38])=[O:36])=[CH:13][C:12]=3[C:18]3[N:19]([CH3:24])[N:20]=[CH:21][C:22]=3[Br:23])[CH:1]([CH2:2][CH2:3]1)[CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27332442,4-DifluorobenzylamineHCID 58964276HCID 58964276, compound

Product 1

HCID 11671294HCID 11671294, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4-[2-(7-Aza-bicyclo[2.2.1]hept-7-yl)-ethoxy]-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenylamine (50.0 mg, 0.13 mmol) was added to a solution of 4-nitrophenylchloroformate (26.0 mg, 0.13 mmol) in 1,2-dichloroethane (4.0 mL) and the mixture stirred at room temperature for 1 hour. To the resulting precipitate mixture was added 2,4-difluorobenzylamine (0.030 mL, 0.25 mmol) and N,N-diisopropylethylamine (0.030 mL, 0.17 mmol), and the mixture stirred an additional 1 hour. The mixture was concentrated and purified by RP-HPLC. The collected fractions were concentrated and 12% sodium hydroxide (aq) (0.2 mL) was added to give pH 9. The solution was extracted into ethyl acetate and the organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to give a white solid (62 mg, 87%). LCMS m/z (%)=560 (M+H79Br, 100), 562 (M+H81Br, 91). 1H NMR (400 MHz, DMSO-d6) δ: 8.59 (bs, 1H), 7.58 (bs, 1H), 7.48-7.38 (m, 2H), 7.29 (bs, 1H), 7.24-7.18 (m, 1H), 7.10-7.04 (m, 2H), 6.60-5.59 (m, 1H), 4.29 (d, J=4.0 Hz, 2H), 4.06-3.96 (m, 2H), 3.64 (s, 3H), 3.11 (bs, 2H), 2.58-2.54 (m, 2H), 1.54-1.52 (m, 4H), 1.15-1.13 (m, 4H).

Workup

  1. stirringthe mixture stirred an additional 1 hour
  2. concentrationThe mixture was concentrated
  3. custompurified by RP-HPLC
  4. concentrationThe collected fractions were concentrated
  5. addition12% sodium hydroxide (aq) (0.2 mL) was added
  6. customto give pH 9
  7. extractionThe solution was extracted into ethyl acetate
  8. dry with materialthe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-e1eb76adaca0464ea8551d9be097c567
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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