Diisopropylethylamine → Tert-butyl 4-(4-(1-(di-tert-butoxyphosphoryloxy)-2-methylpropan-2-ylcarbamoyl)-2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenylthio)phenylcarbamate

HRID 884016Notes

Reaction equation

HRID 884016 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][C:17]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[P:61]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])([O:63][CH2:64][C:65]([NH2:68])([CH3:67])[CH3:66])=[O:62].C(N(CC)C(C)C)(C)C>CS(C)=O.C(OCC)(=O)C>[C:70]([O:69][P:61]([O:63][CH2:64][C:65]([NH:68][C:20]([C:19]1[CH:23]=[CH:24][C:16]([S:15][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:14][CH:13]=2)=[C:17]([NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:37])[CH3:38])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:18]=1)=[O:21])([CH3:67])[CH3:66])([O:74][C:75]([CH3:77])([CH3:76])[CH3:78])=[O:62])([CH3:73])([CH3:72])[CH3:71]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 593768924-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acidHCID 866155662-Amino-2-methylpropyl di-tert-butyl phosphate

Product 1

HCID 67041161Tert-butyl 4-(4-(1-(di-tert-butoxyphosphoryloxy)-2-methylpropan-2-ylcarbamoyl)-2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenylthio)phenylcarbamateYield 62%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Example 89E (100 mg, 0.19 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate [TBTU] (72 mg, 0.22 mmol), the product of Example 95C (65 mg, 0.23 mmol) in DMSO (1 mL) was added N,N-diisopropylethylamine (0.065 mL, 0.37 mmol) dropwise at room temperature under N2. The mixture was stirred at room temperature for 12 hours under N2. The reaction was diluted with ethyl acetate and the organic layer was washed sequentially with water (3×) and brine, dried over MgSO4, and concentrated. The residue was purified by chromatography on silica gel, eluting with a gradient of ethyl acetate in dichloromethane (0-100%) to give the title compound (93 mg, 62%).

Workup

  1. washthe organic layer was washed sequentially with water (3×) and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography on silica gel
  5. washeluting with a gradient of ethyl acetate in dichloromethane (0-100%)

Sources & evidence

ORD record
ord-3124aec104a34b44af94a7e004907223
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

Loading…