Hydrochloric Acid → HCID 178434565, compound

HRID 415955Notes

Reaction equation

HRID 415955 reaction equation
COC(=O)C1C=CC(C2(C#[N:17])CCOCC2)=CC=1.[OH-].[Na+].Cl.C(C1(C2C=CC(C(O)=O)=CC=2)CCOCC1)(=O)N.[CH3:40][O:41][C:42](=[O:63])[C:43]1[CH:48]=[CH:47][C:46]([C:49]2([C:55](=O)[N:56]=[C:57]([N:59](C)C)[CH3:58])[CH2:54][CH2:53][O:52][CH2:51][CH2:50]2)=[CH:45][CH:44]=1.O.NN.C(OC(=O)[NH:73][C:74]1C=[CH:78][C:77]([C:80]2[CH:85]=[CH:84][C:83]([F:86])=[CH:82][CH:81]=2)=[CH:76][C:75]=1N)(C)(C)C>O.CN(C=O)C.CC(O)=O>[NH2:73][C:74]1[CH:75]=[CH:76][C:77]([C:80]2[CH:81]=[CH:82][C:83]([F:86])=[CH:84][CH:85]=2)=[CH:78][C:40]=1[O:41][C:42](=[O:63])[C:43]1[CH:48]=[CH:47][C:46]([C:49]2([C:55]3[NH:17][N:59]=[C:57]([CH3:58])[N:56]=3)[CH2:50][CH2:51][O:52][CH2:53][CH2:54]2)=[CH:45][CH:44]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 59737201Tert-butyl (3-amino-4'-fluoro-[1,1'-biphenyl]-4-YL)carbamateHCID 666188074-(4-Cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl esterHCID 666191534-[4-(1-Dimethylamino-ethylidenecarbamoyl)-tetrahydro-pyran-4-yl]-benzoic acid methyl esterHCID 666191934-(4-Carbamoyl-tetrahydro-pyran-4-yl)-benzoic acid

Product 1

HCID 178434565HCID 178434565, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

4-(4-cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester (300 mg, 1.22 mmol) was suspended in water and then 4N NaOH was added and heated at 110° C. for 15 minutes. To this solution 2N HCl was added to precipitate the product. The solid was filtered out and used for next step without further purification. 4-(4-carbamoyl-tetrahydro-pyran-4-yl)-benzoic acid (200 mg, 0.80 mmol) was dissolved in DMF and then DMA-acetal in excess was added. The mixture was heated at 50° C. for 20 minutes. The reaction mixture was evaporated and used for next step without further purification. 4-[4-(1-dimethylamino-ethylidenecarbamoyl)-tetrahydro-pyran-4-yl]-benzoic acid methyl ester (50 mg, 0.150 mmol) and hydrazine hydrate (0.015 mL, 2 eq) were dissolved in AcOH and heated at 50° C. for 20 minutes. The reaction mixture was evaporated and used for next step without further purification. Hydrolysis HATU coupling, and amine de-protection was carried out following the same procedures from Example 64 using (3-amino-4′-fluoro-biphenyl-4-yl)-carbamic acid tert-butyl ester instead of (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester. MS found for C27H25FN4O3 as (M+H)+ 473.21. 1H NMR (400 MHz, dmso-d6): δ: 13.31 (s, 1H), 9.55 (s, 1H), 7.82 (d, J=7.6 Hz, 2H), 7.50 (dd, J=8.8, 5.2 Hz, 2H), 7.41 (s, 1H), 7.35 (d, J=8.4 Hz, 2H), 7.20 (dd, J=8.0-2.4 Hz, 1H), 7.14 (t, J=8.8 Hz, 2H), 6.77 (d, J=6.77 Hz, 1H), 5.00 (s, 2H), 3.73-3.71 (m, 2H), 3.37-3.31 (m, 2H), 2.58-2.55 (m, 2H), 2.24 (s, 3H), 2.06-2.03 (m, 2H).

Workup

  1. customto precipitate the product
  2. filtrationThe solid was filtered out
  3. customused for next step without further purification
  4. temperatureThe mixture was heated at 50° C. for 20 minutes
  5. customThe reaction mixture was evaporated
  6. customused for next step without further purification
  7. temperatureheated at 50° C. for 20 minutes
  8. customThe reaction mixture was evaporated
  9. customused for next step without further purification
  10. customHydrolysis HATU coupling, and amine de-protection

Sources & evidence

ORD record
ord-9d55189198f9495097b338c22d0b8c8b
Source dataset
uspto-grants-2012_01
Patent number
US08088771B2

Reaction notes

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