Diisopropylethylamine → N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-7-(5-piperidin-1-ylpent-2-ynoyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]-thieno[2,3-d]pyrimidin-4-amine

HRID 1887416Notes

Reaction equation

HRID 1887416 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:29]3[C:28]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[N:30]1([CH2:36][CH2:37][C:38]#[C:39][C:40](O)=[O:41])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CO.C(Cl)Cl.ClCCl.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:29]3[C:28]4[CH2:27][CH2:26][N:25]([C:40](=[O:41])[C:39]#[C:38][CH2:37][CH2:36][N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 117011425-Piperidin-1-yl-pent-2-ynoic acidHCID 59586947[3-Chloro-4-(pyridin-2-ylmethoxy)-phenyl]-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)amine

Product 1

HCID 59586894N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-7-(5-piperidin-1-ylpent-2-ynoyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]-thieno[2,3-d]pyrimidin-4-amineYield 64.4%

Reagents, catalysts & solvents 2

HCID 21226129Dichloromethane methanolSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a suspension of [3-Chloro-4-(pyridin-2-ylmethoxy)-phenyl]-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)amine (0.051 g, 0.00028 mol), 5-Piperidin-1-yl-pent-2-ynoic acid (0.100 g, 0.00023 mol), O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.091 g, 0.00028 mol) in mixture of dichloromethane/tetrahydrofuran (1.2/1.2 ml) was added diisopropylethylamine (0.123 ml, 0.001 mol) slowly over 15 min. The mixture stirred at room temperature for 3 hours. Reaction was judged complete by TLC (Eluent: 10% MeOH/DCM). The reaction mixture was concentrated to dryness under vacuum, dissolved in MeOH (1.5 ml), filtered and subjected to reverse phase HPLC purification to give the desired product (0.087 g, 62.81%)of the desired product. 1H-NMR (CD2Cl2) δ 8.60 (d, 1H), 8.45 (s, 1H), 7.80 (m, 2H), 7.63 (d, 1H), 7.41 (m, 1H), 7.28 (m, 1H), 7.04 (m, 2H), 5.25 (s, 2H), 4.98 (d, 2H), 4.05 (dd, 2H), 3.10 (d, 2H), 2.60 (m, 4H), 2.40 (m, 4H), 1.62 (m, 4H), 1.45 (m, 2H); LCMS RT=2.37 min; [M+H]+=587.1.

Workup

  1. customReaction
  2. concentrationThe reaction mixture was concentrated to dryness under vacuum
  3. dissolutiondissolved in MeOH (1.5 ml)
  4. filtrationfiltered
  5. customphase HPLC purification

Sources & evidence

ORD record
ord-0758778a6d974919b3ac6040e1625418
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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