Sodium Hydroxide → HCID 71258372, compound

HRID 1630323Notes

Reaction equation

HRID 1630323 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].[CH3:33][C:34]([CH3:39])([CH3:38])[CH2:35][CH2:36][NH2:37].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:37][CH2:36][CH2:35][C:34]([CH3:39])([CH3:38])[CH3:33])[CH:28]=2)[C:17]=1[C:18]1[CH2:23][CH2:22][C:21]([CH3:24])([CH3:25])[CH2:20][CH:19]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 197093,3-DimethylbutylamineHCID 81531DiisopropylethylamineHCID 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 71258372HCID 71258372, compoundYield 66.5%

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 3,3-dimethylbutan-1-amine (13.69 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-(2-((3,3-dimethylbutyl)carbamoyl)-7-(4,4-dimethylcyclohex-1-en-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (23.6 mg, 0.045 mmol, 66.5% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.96 (t, J=5.8 Hz, 1H), 6.88 (s, 1H), 6.26 (br. s., 0.6H), 5.85 (br. s., 0.4H), 5.38 (s, 0.6H), 5.28 (s, 0.4H), 3.37-3.28 (m, 4H), 2.66 (s, 1H), 2.59 (s, 2H), 2.19-1.97 (m, 2H), 1.68-1.50 (m, 2H), 1.47 (t, J=7.9 Hz, 2H), 1.19 (s, 3H), 1.15 (s, 6H), 1.12 (s, 3H), 1.07 (s, 3H), 0.94 (s, 9H). LCMS (M+H)=499.4.

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-d8b0d90cce714281a531439be090d1f4
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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