Water → HCID 118447905, compound

HRID 1775481Notes

Reaction equation

HRID 1775481 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:40][C@H:41]1[CH2:46][O:45][CH2:44][CH2:43][N:42]1[C:47]1[N:48]=[C:49]([C:62]2[CH:63]=[N:64][C:65]([NH2:68])=[N:66][CH:67]=2)[C:50]2[CH2:55][CH2:54][N:53]([C@@:56]3([CH3:61])[CH2:60][CH2:59][NH:58][CH2:57]3)[C:51]=2[N:52]=1.O>CN(C=O)C>[NH2:68][C:65]1[N:66]=[CH:67][C:62]([C:49]2[C:50]3[CH2:55][CH2:54][N:53]([C@@:56]4([CH3:61])[CH2:60][CH2:59][N:58]([C:10](=[O:12])[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:14])[CH3:13])[CH2:57]4)[C:51]=3[N:52]=[C:47]([N:42]3[CH2:43][CH2:44][O:45][CH2:46][C@@H:41]3[CH3:40])[N:48]=2)=[CH:63][N:64]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118436287HCID 118436287, compound

Product 1

HCID 118447905HCID 118447905, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-tert-butoxycarbonylamino-2-methyl-propionic acid (728 mg, 3.58 mmol) in anhydrous DMF (13.8 mL) at 0° C. was added HATU (1570 mg, 4.13 mmol) portionwise, and the mixture was stirred at 0° C. for 40 min. 5-{2-[(3S)-3-methylmorpholin-4-yl]-7-[(3S)-3-methylpyrrolidin-3-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amine hydrochloride (1294 mg, 2.757 mmol) and TEA (1.92 ml, 13.8 mmol) were added and the reaction mixture was stirred at room temperature for 2 h. Water was added, the mixture was extracted with EtOAc (3 times), the combined organic layers were washed with brine, and dried over Na2SO4. The residue was purified via ISCO silica gel chromatography (40 g column) using a gradient of 0-100% EtOAc containing 10% MeOH/EtOAc to give the title compound (1247 mg, 78%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 2 H), 6.59 (br s, 3 H), 4.67-4.54 (m, 1 H), 4.23 (d, J=11.5 Hz, 1 H), 3.92 (d, J=14.2 Hz, 1 H), 3.83 (d, J=11.4 Hz, 1 H), 3.70-3.40 (m, 7 H), 3.22-3.05 (m, 6 H), 2.12-2.02 (m, 1 H), 1.37 (s, 9 H), 1.35 (s, 6 H), 1.31 (s, 3 H). m/z (APCI+) for C29H43N9O4 582.7 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 h
  2. extractionthe mixture was extracted with EtOAc (3 times)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe residue was purified via ISCO silica gel chromatography (40 g column)

Sources & evidence

ORD record
ord-a52a3efe15b34945bbe1a7c0ab0afe9e
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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