Glyoxylic Acid → Hydrochloric Acid

HRID 1628262Notes

Reaction equation

HRID 1628262 reaction equation
[CH:1]([N:4]1[C:8]([NH2:9])=[CH:7][C:6]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[N:5]1)([CH3:3])[CH3:2].[C:16]([NH:23][C@H:24]([C:33]([OH:35])=O)[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)(OC(C)(C)C)=O.[C:36]([OH:40])(=[O:39])C=O>>[Cl:32][C:29]1[CH:28]=[CH:27][C:26]([CH2:25][C@H:24]([NH:23][CH2:16][C:36]([OH:40])=[O:39])[C:33]([NH:9][C:8]2[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[C:6]([C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)[CH:7]=2)=[O:35])=[CH:31][CH:30]=1.[ClH:32]

Participants

5

Reactant 3

HCID 760Glyoxylic AcidHCID 2734499N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanineHCID 674960761-isopropyl-3-(pyridin-4-yl)-1H-pyrazol-5-amine

Product 2

HCID 313Hydrochloric AcidYield 14%HCID 67497229(S)-2-(3-(4-Chlorophenyl)-1-(1-isopropyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid

Procedure

This title compound was prepared starting from 29.B (169 mg, 0.84 mmol) and Boc-4-chloro L-phenylalanine (available from Chem-Impex International, Inc. (305 mg, 1.0 mmol) according the procedure described above for conversion of 17.B to 17.2, except that glyoxylic acid (1.0 equiv.) was used in the last step. After purification by preparative HPLC (5-40% CH3CN/water, 45 min), product fractions were collected, treated with 1.0 N HCl, and concentrated to provided 29 HCl salt as colorless solid (52 mg, 14%). MS ESI (positve.) m/e: 442.1 (M+H); 1H NMR (400 MHz, CD3OD) δ ppm 8.77 (d, J=7.04 Hz, 2H), 8.40 (d, J=7.04 Hz, 2H), 7.39-7.49 (m, 2H), 7.32-7.39 (m, 2H), 7.08 (s, 1H), 4.58 (dd, J=10.17, 5.87 Hz, 1H), 4.06 (s, 2H) 3.99 (quin, J=6.55 Hz, 1H), 3.49 (dd, J=13.30, 5.87 Hz, 1H), 3.23 (dd, J=13.30, 9.78 Hz, 1H), 2.32 (s, 1H), 1.38 (dd, J=10.96, 6.26 Hz, 6H).

Workup

  1. customThis title compound was prepared
  2. customAfter purification by preparative HPLC (5-40% CH3CN/water, 45 min), product fractions
  3. customwere collected
  4. additiontreated with 1.0 N HCl
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4b9065554c9445e293687efc13e2cdfb
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

Loading…