Dimethylamine → HCID 57546025, compound

HRID 913927Notes

Reaction equation

HRID 913927 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:21][O:22][CH:23]([C:27]2[C:35]3[C:31](=[CH:32][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:34]=3)[CH:30]=[C:29]([Cl:44])[CH:28]=2)[C:24](O)=[O:25])([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:45][NH:46][CH3:47].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O>[Cl:44][C:29]1[CH:28]=[C:27]([CH:23]([O:22][CH2:21][C:11]2([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)[C:24]([N:46]([CH3:47])[CH3:45])=[O:25])[C:35]2[C:31](=[CH:32][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:34]=2)[CH:30]=1

Participants

5

Reactant 3

HCID 674DimethylamineHCID 2724699PyBOPHCID 57546162HCID 57546162, compound

Product 1

HCID 57546025HCID 57546025, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-((1-(tert-butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methoxy)-2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acid (25 mg, 0.039 mmol) and dimethylamine (40% in water, 0.024 mL) in dimethylformamide (1 mL) at 0° C. was added PyBOP® (24.08 mg, 0.046 mmol). The ice bath was removed and stirring continued for 1 h. The reaction was quenched by addition of water and diluted with diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (50%→85% ethyl acetate/n-hexane) gave 21 mg (81%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.31 (dd, J=8.5, 5.5 Hz, 2H), 7.09 (d, J=1.8 Hz, 1H), 6.99 (dd, J=8.6, 8.5 Hz, 2H), 5.66 (d, J=10.7 Hz, 1H), 5.62 (d, J=10.7 Hz, 1H), 3.70 (m, 2H), 3.57 (m, 3H), 3.44 (d, J=8.9 Hz, 1H), 3.05 (m, 2H), 2.88 (s, 3H), 2.80 (s, 3H), 2.13 (m, 2H), 1.91 (m, 2H), 1.42 (s, 9H), 0.91 (t, J=8.3 Hz, 2H), −0.04 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 169.0, 161.5 (d, J=245 Hz), 155.0, 145.8, 138.7, 129.0 (d, J=7.7 Hz), 128.3, 125.9, 122.7, 122.5, 119.2, 115.2 (d, J=21 Hz), 82.1, 79.4, 78.4, 75.7, 67.7,41.4, 40.1 (br), 36.8, 36.1, 32.1, 28.6, 17.9, −1.3. Mass spec.: 675.38 (MH)+.

Workup

  1. customThe ice bath was removed
  2. customThe reaction was quenched by addition of water
  3. additiondiluted with diethyl ether
  4. washThe ethereal was washed with water (2×)
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (50%→85% ethyl acetate/n-hexane) gave 21 mg (81%) as a foam solid

Sources & evidence

ORD record
ord-33813c2922b14b8aadff7e88f801ba7f
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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