Diisopropylethylamine → HCID 66851473, compound

HRID 1466603Notes

Reaction equation

HRID 1466603 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:17]([C:18]([OH:20])=O)=[C:12]2[N:13]=[CH:14][CH:15]=[CH:16][N:11]2[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([O:35][CH3:36])=[C:26]([C:28]2[N:32](C)[N:31]=[CH:30][C:29]=2[NH2:34])[CH:27]=1.[CH:37](N(CC)C(C)C)(C)C.C1CN([P+](ON2N=NC3C=CC=NC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C1C=CN=CC=1.CN(C=O)C.CCOC(C)=O>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([O:35][CH3:36])=[C:26]([C:28]2[C:29]([NH:34][C:18]([C:17]3[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[N:13][C:12]=34)=[O:20])=[CH:30][N:31]([CH3:37])[N:32]=2)[CH:27]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 66851217HCID 66851217, compoundHCID 66851504HCID 66851504, compound

Product 1

HCID 66851473HCID 66851473, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(tert-butoxycarbonylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (88 mg, 0.32 mmol), 5-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-amine (75 mg, 0.32 mmol), 4-dimethylaminopyridine (7.7 mg, 0.063 mmol), and N,N-diisopropylethylamine (0.16 mL, 0.95 mmol) in DMF (3 mL) was added PyAOP (200 mg, 0.38 mmol). The reaction mixture was stirred for 14 hrs at 50° C., then diluted with EtOAc. The organic layer was washed twice with water, and once with brine, then dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography, eluting with EtOAc to afford 98 mg (62%) of tert-butyl 3-(3-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)pyrazolo[1,5-a]pyrimidin-2-ylcarbamate. 1H NMR (400 MHz, CDCl3) δ 9.85 (s, 1H), 9.65 (s, 1H), 8.76 (dd, J=6.8, 1.7, 1H), 8.44 (dd, J=4.3, 1.7, 1H), 8.20 (s, 1H), 7.56 (d, J=2.7, 1H), 7.36 (dd, J=8.8, 2.7, 1H), 6.97 (d, J=8.9, 1H), 6.90 (dd, J=6.9, 4.3, 1H), 3.97 (s, 3H), 3.87 (s, 3H), 1.56 (s, 9H).

Workup

  1. washThe organic layer was washed twice with water
  2. dry with materialonce with brine, then dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with EtOAc

Sources & evidence

ORD record
ord-1c712bd5f7d04571b2ff5ac63fdc9068
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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