Ammonia → tert-butyl 4-((2-amino-1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913929Notes

Reaction equation

HRID 913929 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].N.C1C[N:49]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O>[NH2:49][C:24](=[O:25])[CH:23]([C:27]1[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]=[C:29]([Cl:44])[CH:28]=1)[O:22][CH2:21][C:11]1([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 2724699PyBOPHCID 57546162HCID 57546162, compound

Product 1

HCID 57546167tert-butyl 4-((2-amino-1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

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 (100 mg, 0.154 mmol) and ammonia (7 M in methanol, 0.110 mL, 0.771 mmol) in dimethylformamide (2 mL) at 0° C. was added PyBOP (96 mg, 0.19 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 89 mg (89%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.02 (s, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.27 (dd, J=8.9, 5.2 Hz, 2H), 7.00 (dd, J=8.6, 8.5 Hz, 2H), 6.95 (d, J=1.5 Hz, 1H), 6.48 (d, J=2.7 Hz, 1H), 6.05 (d, J=2.4 Hz, 1H), 5.65 (s, 2H), 5.23 (s, 1H), 3.66 (m, 2H), 3.60 (t, J=8.1 Hz, 2H), 3.51 (d, J=8.9 Hz, 1H), 3.41 (d, J=8.9 Hz, 1H), 3.01 (m, 2H), 2.10 (m, 2H), 1.80 (m, 2H), 1.40 (s, 9H), 0.91 (m, 2H), −0.05 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 172.5, 161.5 (d, J=246 Hz), 155.0, 146.1, 138.42, 138.39, 128.7 (d, J=7.7 Hz), 128.5, 127.8, 125.5, 122.9, 122.6, 119.7, 115.4 (d, J=21 Hz), 82.1, 79.5, 78.3, 67.8, 41.2, 40.0 (br), 32.2, 32.1, 28.5, 17.9, −1.3. Mass spec.: 647.35 (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 89 mg (89%) as a foam solid

Sources & evidence

ORD record
ord-1b12893c6520487ba496f536ef6a5ff1
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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