Diisopropylethylamine → methyl 1-(4-fluorobenzyl)-3-(3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamido)cyclohexanecarboxylate

HRID 530875Notes

Reaction equation

HRID 530875 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([OH:19])=O)[CH:15]=3)[N:10]([C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:39][CH:40]1[CH2:45][CH2:44][CH2:43][C:42]([CH2:50][C:51]2[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=2)([C:46]([O:48][CH3:49])=[O:47])[CH2:41]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O>[F:57][C:54]1[CH:53]=[CH:52][C:51]([CH2:50][C:42]2([C:46]([O:48][CH3:49])=[O:47])[CH2:43][CH2:44][CH2:45][CH:40]([NH:39][C:17]([C:14]3[CH:15]=[C:16]4[C:11](=[CH:12][CH:13]=3)[N:10]([C:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:9]=[C:8]4[C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)=[O:19])[CH2:41]2)=[CH:56][CH:55]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67983392Methyl 3-amino-1-(4-fluorobenzyl)cyclohexanecarboxylateHCID 679849753-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxylic acid

Product 1

HCID 67985845methyl 1-(4-fluorobenzyl)-3-(3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamido)cyclohexanecarboxylateYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a flask, 3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxylic acid (567 mg, 1.15 mmol), methyl 3-amino-1-(4-fluorobenzyl)cyclohexanecarboxylate (1.09 mmol), and HATU (622 mg, 1.64 mmol) was dissolved in dimethylformamide (3 mL). The reaction mixture was stirred for 2 minutes at room temperature. Diisopropylethylamine (0.95 mL, 5.45 mmol) was added to the reaction. The reaction was allowed to stir for an additional 1 hr. Upon completion, the reaction was quenched with water (5 mL). The water layer was extracted with ethyl acetate (20 mL) three times. The organic fractions were combined, dried with sodium sulfate, and concentrated to yield the crude product. The crude compound was purified using flash chromatography (0-100% ethyl acetate in hexane gradient) to give the title compound (690 mg).

Workup

  1. stirringto stir for an additional 1 hr
  2. customUpon completion, the reaction was quenched with water (5 mL)
  3. extractionThe water layer was extracted with ethyl acetate (20 mL) three times
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. customto yield the crude product
  7. customThe crude compound was purified

Sources & evidence

ORD record
ord-181dd0956820485987ff188e2a5d952a
Source dataset
uspto-grants-2016_05
Patent number
US09351965B2

Reaction notes

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