Dimethylformamide → HCID 59593015, compound

HRID 2262251Notes

Reaction equation

HRID 2262251 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][NH2:12])=[CH:8][C:6]=2[N:7]=1.[C:19]([OH:29])(=O)[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1.CN(C(ON1N=N[C:40]2[CH:41]=CC=N[C:39]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:56]([CH:60]([CH3:62])[CH3:61])C(C)C.NO.O.[CH3:66][N:67](C=O)C>C([O-])(O)=O.[Na+]>[NH:56]1[C:60]2[C:61](=[C:39]([C:2]3[N:3]=[C:4]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[C:5]4[S:10][C:9]([CH2:11][NH:12][C:19](=[O:29])[C:20]5[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=5)=[CH:8][C:6]=4[N:7]=3)[CH:40]=[CH:41][CH:62]=2)[CH:66]=[N:67]1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 74784-Methoxybenzoic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22235265HCID 22235265, compoundHCID 46180727(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine

Product 1

HCID 59593015HCID 59593015, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
40 °C

Procedure

(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine 27 from Example 11 (50.0 mg, 0.17 mM) was dissolved in 1.5 mL DMF. To this was added 77.6 mg (3.0 eq) of p-anisic acid, 129.3 mg (2.0 eq) HATU and 0.18 uL (6.0 eq) DIPEA and the reaction heated at 40° C. for 18 hours. Complete reaction was confirmed by HPLC and 2.0 eq NH2OH—H2O was added to the cooled reaction and the reaction stirred for ten minutes. The reaction was diluted with sat. NaHCO3, extracted with EtOAc, washed with brine, dried over MgSO4 and concentrated in vacuo. This intermediate was purified by flash chromatography (EtOAc/Hexanes) followed by Suzuki coupling of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-indazole 7 as per General Procedure A. Complete reaction was confirmed by LCMS and the reaction was concentrated in vacuo to give 18.9 mg of 363 after RP-HPLC purification (38% yield). MS (Q1) 501.3 (M)+

Workup

  1. customComplete reaction
  2. additionwas added to the cooled reaction
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThis intermediate was purified by flash chromatography (EtOAc/Hexanes)
  8. customComplete reaction
  9. concentrationthe reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-e43c503a96b94a4e8bb064ada4e31e45
Source dataset
uspto-grants-2010_12
Patent number
US07846929B2

Reaction notes

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