Formic Acid → HCID 71236956, compound

HRID 2280805Notes

Reaction equation

HRID 2280805 reaction equation
[OH:1][C@H:2]1[C@H:7]([CH3:8])[CH2:6][CH2:5][C@@H:4]([NH:9][C:10]2[C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=[C:12](S(C)(=O)=O)[N:11]=2)[CH2:3]1.[C@@H:23]([NH2:27])([CH2:25][CH3:26])[CH3:24].C(O)=O.C(=O)(O)[O-]>CN(C=O)C>[C@@H:23]([NH:27][C:12]1[N:11]=[C:10]([NH:9][C@@H:4]2[CH2:5][CH2:6][C@@H:7]([CH3:8])[C@H:2]([OH:1])[CH2:3]2)[C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=1)([CH2:25][CH3:26])[CH3:24]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 769Bicarbonate IonHCID 67137532-Butanamine, (S)-HCID 71237514HCID 71237514, compound

Product 1

HCID 71236956HCID 71236956, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirring suspension of 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(methylsulfonyl)pyrimidine-5-carboxamide (0.2 g, 0.609 mmol) in DMF (3 mL) was added (S)-(+)-sec-butylamine (0.305 mL, 3.05 mmol) and the reaction was heated to 90° C. overnight. The crude reaction mixture was concentrated under reduced pressure and then purified using reverse-phased semi-preparative HPLC (5-75% methanol+0.1% formic acid in water+0.1% formic acid, over 26 min). Fractions containing product were concentrated under reduced pressure and the resulting residue was redissolved in methanol (5 mL), passed over a Varian StratoSpheres HCO3 resin SPE tube for formic acid removal (0.9 mmol bicarbonate equiv.), and then concentrated under reduced pressure to afford 2-((S)-sec-butylamino)-4-(((1R,3R,4R)-3-hydroxy-4-methylcyclohexyl)amino)pyrimidine-5-carboxamide (0.129 g, 0.402 mmol, 66% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80-1.24 (m, 15H) 1.35-1.45 (m, 1H) 1.54 (br. s., 1H) 1.66 (d, J=12.89 Hz, 1H) 1.92 (br. s., 1H) 2.14 (br. s., 1H) 2.97 (br. s., 1H) 3.71-3.99 (m, 1H) 4.55 (d, J=5.86 Hz, 1H) 6.96 (br. s., 1H) 8.34 (s, 1H) 8.90 (br. s., 1H); MS (ESI) m/z 322.5 [M+1]+.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. custompurified
  4. customreverse-phased semi-preparative HPLC (5-75% methanol+0.1% formic acid in water+0.1% formic acid, over 26 min)
  5. additionFractions containing product
  6. concentrationwere concentrated under reduced pressure
  7. dissolutionthe resulting residue was redissolved in methanol (5 mL)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fa018da44c32486e9a34e1b74664929b
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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