Diisopropylethylamine → Tert-butyl 4-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinoyl)piperazine-1-carboxylate

HRID 2065577Notes

Reaction equation

HRID 2065577 reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=3)[C:22]([OH:24])=O)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:60]([N:67]1[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]1)([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61]>CN(C=O)C>[F:26][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=3)[C:22]([N:70]3[CH2:69][CH2:68][N:67]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:72][CH2:71]3)=[O:24])=[N:14][CH:15]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581719845-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinic acid

Product 1

HCID 67366920Tert-butyl 4-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinic acid 19 (0.028 mmol) in DMF (1 mL) is added HATU (0.033 mmol) and DIEA (0.084 mmol) at rt. The resulting mixture is stirred for 2 min then N-boc-piperazine (0.03 mmol) is added. The reaction mixture is stirred at it for 12 h and directly purified by preparative LCMS to give tert-butyl 4-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinoyl)piperazine-1-carboxylate. The residue is treated with TFA (1 mL) at rt for 1 h, concentrated under vacuum, and directly purified by preparative LCMS to afford (5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)pyridin-3-yl)(piperazin-1-yl)methanone B3. NMR (400 MHz, d3-CH3CN) δ 9.32 (bs, 1H), 8.86 (s, 2H), 8.67 (bs, 1H), 8.41 (bs, 1H), 7.75 (d, J=12.0 Hz, 2H), 7.33 (d, J=12.0 Hz, 2H), 6.87 (t, J=73 Hz, 1H), 4.20 (bs, 4H), 3.30 (bs, 4H). MS (m/z) (M+1)+: 427.1.

Workup

  1. stirringThe reaction mixture is stirred at it for 12 h
  2. customdirectly purified by preparative LCMS

Sources & evidence

ORD record
ord-9cc4212dd6734060978976bbeeca26e2
Source dataset
uspto-grants-2012_10
Patent number
US08288540B2

Reaction notes

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