Sodium Hydroxide → HCID 71259120, compound

HRID 1630322Notes

Reaction equation

HRID 1630322 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:32])=[N:14][C:15]2[N:16]([N:26]=[C:27]([C:29](O)=[O:30])[CH:28]=2)[C:17]=1[C:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][NH2:41])=[CH:36][C:35]=1[CH3:42].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.CO.O>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:32])=[N:14][C:15]2[N:16]([N:26]=[C:27]([C:29](=[O:30])[NH:41][CH2:40][C:37]3[CH:38]=[CH:39][C:34]([F:33])=[C:35]([CH3:42])[CH:36]=3)[CH:28]=2)[C:17]=1[C:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=1)[C:7]([OH:9])=[O:8])([CH3:3])([CH3:2])[CH3:4]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2774599(4-Fluoro-3-methylphenyl)methanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71259112HCID 71259112, compound

Product 1

HCID 71259120HCID 71259120, compoundYield 43.2%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (S)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylcyclohex-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (30 mg, 0.068 mmol) and (4-fluoro-3-methylphenyl)methanamine (18.83 mg, 0.135 mmol) in DMF (1.5 mL) was added DIEA (0.059 mL, 0.338 mmol), HATU (51.4 mg, 0.135 mmol) and DMAP (1.653 mg, 0.014 mmol) and the resulting mixture was stirred at room temp for 16 h. At this point LCMS indicated completion of reaction. Water was then added and the mixture was extracted with ether (25 mL), washed with brine (15 mL), dried (Na2SO4), filtered and concentrated. Crude was then treated with 1N NaOH (0.203 mL, 0.203 mmol) in MeOH (1.500 mL) at 60° C. for 5 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(7-(4,4-dimethylcyclohex-1-en-1-yl)-2-((4-fluoro-3-methylbenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (16.5 mg, 0.029 mmol, 43.2% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.58 (t, J=6.0 Hz, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.19 (dd, J=8.2, 5.2 Hz, 1H), 7.12-7.06 (m, 1H), 6.92 (s, 1H), 6.33 (br. s., 0.7H), 5.85 (br. s.; 0.3H), 5.31 (br. s., 0.7H), 5.23 (br. s., 0.3H), 4.54-4.39 (m, 2H), 2.67 (br. s., 1H), 2.59 (s, 2H), 2.23 (d, J=1.5 Hz, 3H), 2.14-2.10 (m, 4H), 1.70-1.59 (m, 2H), 1.18 (br. s., 3H), 1.14 (s, 7H), 1.08 (br. s., 2H), 1.07 (br. s., 4H). LCMS (M+H)=537.5.

Workup

  1. customcompletion of reaction
  2. extractionthe mixture was extracted with ether (25 mL)
  3. washwashed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. temperatureMixture was then cooled
  8. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-74b32194bd4d45dba16e0420de3ba32f
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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