Hydrochloric Acid → HCID 22051053, compound

HRID 1867121Notes

Reaction equation

HRID 1867121 reaction equation
C([NH:8][CH2:9][C:10](O)=[O:11])(OC(C)(C)C)=O.CN(C=O)C.Cl.[NH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([F:46])=[C:25]([N:27]2[C:32]([CH3:33])=[CH:31][C:30]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=3[F:43])=[C:29]([Cl:44])[C:28]2=[O:45])[CH:26]=1.Cl>CO>[ClH:44].[Cl:44][C:29]1[C:28](=[O:45])[N:27]([C:25]2[CH:26]=[C:21]([CH:22]=[CH:23][C:24]=2[F:46])[CH2:20][NH:19][C:10](=[O:11])[CH2:9][NH2:8])[C:32]([CH3:33])=[CH:31][C:30]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=1[F:43]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 22050116HCID 22050116, compound

Product 1

HCID 22051053HCID 22051053, compoundYield 130.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A 25 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with boc-glycine (105 mg, 0.6 mmol) and 8 mL of DMF. The mixture was cooled to 0° C. and isboutylchloroformate (77.5 μL, 0.6 mmol) was added and stirred for 20 min. 1-[5-(aminomethyl)-2-fluorophenyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one hydrochloride (250 mg, 0.6 mmol) was added and stirred for 3 h. After completion of the reaction by LC-MS, concentrated HCl (2 mL) and 2 mL of methanol was added to remove the boc group. The reaction was stirred for 24 h, neutralized with 2M NaOH and extracted with ethyl acetate. The organic phase was dried with Na2SO4 and concentrated in vacuo to obtain (196 mg, 66%) of the desired product as a the HCl salt. 1H NMR (400 MHz, (CD3OD) δ 7.6 (q, J=8 and 6.5 Hz, 1H), 7.5 (m, 1H), 7.3 (m, 2H), 7.0 (m, 2H), 6.63 (s, 1H), 5.35 (s, 2H), 4.4 (q, J=15 and 13.6 Hz, 2H), 3.7 (s, 2H), 2.05 (s, 3H) ppm. ES-HRMS m/z 466.1157 (M+H calcd for C22H20ClF3N3O3 requires 466.1140).

Workup

  1. customA 25 mL round bottomed flask equipped with stirbar and nitrogen inlet
  2. additionisboutylchloroformate (77.5 μL, 0.6 mmol) was added
  3. stirringstirred for 3 h
  4. additionwas added
  5. customto remove the boc group
  6. stirringThe reaction was stirred for 24 h
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic phase was dried with Na2SO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-94921e7ab23a4c55baa602480a9e5ff2
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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