2-Amino-2-methyl-1-propanol → 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(1-hydroxy-2-methylpropan-2-yl)benzamide

HRID 1049890Notes

Reaction equation

HRID 1049890 reaction equation
[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([OH:17])=O)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.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.[NH2:55][C:56]([CH3:60])([CH3:59])[CH2:57][OH:58].C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([NH:55][C:56]([CH3:60])([CH3:59])[CH2:57][OH:58])=[O:17])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 118072-Amino-2-methyl-1-propanolHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 727035203-(4-Aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluorobenzoic acid

Product 1

HCID 727035213-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(1-hydroxy-2-methylpropan-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-benzoic acid (100 mg, 0.35 mmol) 3 in DMF was treated with DIPEA (0.3 mL, 1.76 mmol) followed by HATU (279 mg, 0.7 mmol). The mixture was stirred at room temperature for 10 minutes, then 2-amino-2-methyl-propan-1-ol, (CAS-124-68-5) (0.07 mL, 0.7 mmol) was added and continue stirred at room temperature overnight. Saturated sodium bicarbonate was added, and the mixture was extracted with EtOAc. The combined organics were dried over sodium sulfate and concentrated. The crude was purified by Prep HPLC to give 15 mg of 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(1-hydroxy-2-methylpropan-2-yl)benzamide 4. LC/MS (ESI+): m/z 356 (M+H). 1H NMR (400 MHz, DMSO) δ 8.55 (t, J=8.7 Hz, 1H), 8.47 (s, 1H), 8.44 (d, J=7.1 Hz, 1H), 8.18 (t, J=8.8 Hz, 1H), 7.82 (d, J=24.4 Hz, 1H), 7.71 (d, J=9.4 Hz, 1H), 4.87 (t, J=6.0 Hz, 1H), 3.58 (d, J=5.8 Hz, 2H), 2.07 (s, 2H), 1.36 (s, 6H).

Workup

  1. stirringcontinue stirred at room temperature overnight
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude was purified by Prep HPLC

Sources & evidence

ORD record
ord-00ed1b17e9de43dfaacc70bbc35591a1
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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